Sean Moloughney07.01.09
As FDA gears up to enforce GMP standards that took effect in June for dietary supplement manufacturers with 20 employees or more, experts claim that nutraceutical testing has never been so important to the industry's future.
In light of several recent high profile cases, such as the Hydroxycut recall, the spiking of protein with melamine, and the peanut butter/salmonella scare that led to massive product recalls, quality and safety have become critical factors in the maturation of the nutraceuticals market.
"You can't measure quality without testing," said Ed Wyszumiala, general manager, Dietary Supplements, Functional Foods and Athletic Banned Substances Certification Programs, NSF International, Ann Arbor, MI. "The demand for safer, quality dietary supplement products among consumers and athletes, combined with new FDA guidelines, have raised the bar for the manufacturing and production of supplements. As a result, purity testing has been a top priority for dietary supplement and ingredient manufacturers that are committed to communicating the integrity of their products."
Testing will continue to be an important and ever-present part of doing business, according to William Neumann, vice president, Quality & Regulatory Affairs, Consumer Product Testing Co., Inc. (CPTC), Fairfield, NJ. "Good nutraceutical companies perform sufficient testing to assure that quality requirements are met at all stages up and down the supply chain."
Quality assurance requires several levels of testing, Mr. Neumann said, including "physical testing (e.g., tablet hardness, weight variation of dosage units, disintegration and dissolution); analytical testing (e.g., assay of active ingredients and chemical impurities); and microbial testing (e.g., bacterial count and the presence of pathogens)."
"Such testing utilizes a wide range of techniques and methodologies and is typically performed on incoming raw materials, in-process batch samples, finished product batch samples, validation samples and stability samples," he added.
Raw material identification is the first and most important test in satisfying GMPs for quality control, according to Elan Sudberg, lab manager, Alkemists Pharmaceuticals, Costa Mesa CA. "It makes no sense testing for anything before confirming the identity of an ingredient."
Common and accepted identification methods include organoleptic analysis, microscopy, infrared (IR) technology, high performance liquid chromatography (HPLC) and/or gas chromatography (GC).
"Due to the highly complicated matrix and variability of botanical extracts and raw material in the marketplace, an extensive library of reference materials and methods is crucial to reliably identify such material with any of these techniques," said Mr. Sudberg.
Experts often point to the importance of validating analytical test methods, but interestingly, Frank Jaksch, president and CEO, ChromaDex, Irvine, CA, noted that GMPs don't call for compendial or validated standards. "The rule is very specific and calls for 'scientifically valid' methods. It means they want to see you're using some rationale for choosing the best method."
However, Mr. Sudberg said that as an analytical lab, Alkemists receives specification sheets accompanying dietary supplements stating certain levels of constituents without noting methodology to reflect the source of data. "It is very difficult to extract methodology from companies overseas or even on this continent due to the mysterious proprietary methods of manufacturers," he said. "If specs are to be confirmed, it would help to have the methodology used by the ingredient manufacturer for third party verification."
Mr. Jaksch used stevia as an example of the variance among similar products in the market. "There are guys out there selling 97%, 98% and even 99% stevia," he noted. "Well, what does that really mean? How did you get that number? Depending on the method you use you can get a significant variance of numbers. And companies will use that to basically play games."
Carlos Navarro, marketing manager, Eurofins Scientific, Metairie, LA, agreed that efforts to standardize methods should be a point of focus. "There are so many methods out there it requires a great amount of diligence to have things validated," he said.
While GMPs don't call specifically for compendial standards, they do stipulate that companies must conduct identity testing on every lot of every raw material, said Darryl Sullivan, associate director, Scientific Affairs & Analytical Services, Covance Laboratories, Madison, WI. "I see a lot of people trying to do some sort of 'quick and dirty' identification testing. We need some better validation around those test methods and we probably need to put some more rigor around that."
James Griffiths, vice president, Food, Dietary Supplement & Excipient Standards, U.S. Pharmacopeia (USP), Rockville, MD, agreed that more companies should invest energy and ideas into how they can effectively authenticate their materials. "Maybe it's a mixture of two or three analyzers in tandem, each of which use a more simplified method, but together give a high level of confidence that my stuff is my stuff," he said.
Among many other challenges in the testing arena, laboratories must also find low-level contaminants that originate from the environment, manufacturing process or storage containers. "This includes primary pollutants, residual solvents, agrochemicals, veterinary drugs and chemical species found in 'plastic' containers," said CPTC's Mr. Neumann. "The sensitivity and accuracy that such testing requires is resulting in an increased dependence upon mass spectrometry."
Especially in an age where intentional, economically motivated adulteration jeopardizes the health and safety of consumers, as well as the overall credibility of the industry, those in the testing arena need to be more proactive, according to USP's Mr. Griffiths. "We're going to run ourselves ragged looking for the next melamine, because the bad guys are always going to be one step ahead," he said. "Let's have a protein analyzer, not a melamine analyzer. Acetaminophen, bilberry, sucrose-all these things need to be addressable from the authenticated substance, not the adulterant du jour. You're going to bankrupt yourself or drive yourself crazy trying to always be reactive in this environment."
Mr. Sullivan of Covance agreed that adulteration demands attention. "What sort of preventive testing can we do to guard against the next adulterant? We need to be able to respond to something that comes along, validate those test methods and produce data quickly. In my laboratory world that's one of the big challenges we face."
As consumers continue to seek out less costly products given current economic conditions, "the time will remain ripe for the bad guys to swoop in and skim something off before the next crisis and then move on," Mr. Griffiths added.
Such activity also leaves credible companies operating under best practices vulnerable to guilt by association. "I think the last couple of food scandals illustrated the point that if there is one bad player the whole segment suffers," said Markus Lipp, director of food standards with USP.
Mr. Navarro of Eurofins also said there has been a greater push toward ensuring food safety. "More companies are starting to think about it, whether they're doing it in house or subbing it out to testing companies," he noted.
In order to stand apart from those who don't hold the best interest of consumers in mind, NSF's Mr. Wyszumiala said, "It's important that companies have their ingredients tested and certified by an accredited, independent, third-party organization such as NSF, as well as have their facility GMP registered."
Given the attention paid to recent cases, consumers have also become very conscious of quality issues in today's marketplace, said Mr. Sudberg, of Alkemists Pharmaceuticals. "Over the last three to four years numerous product recalls and contamination issues have empowered consumers to be more informed of what level of quality assurance/control to expect from a product."
For example, label claim verification has become another critical component of nutraceutical testing, as independent watchdogs like ConsumerLab.com continue to evaluate and publish results about finished products. "In terms of verifying label claims, GMPs are clear that is going to be a major requisite," said Mr. Navarro.
So, given increased focus on testing, are companies prepared to comply with GMP requirements? And how will regulation impact the industry landscape?
Most experts seem to agree that while larger companies-many of which have modeled their operations after pharmaceutical companies-have prepared themselves for GMP compliance, others have done very little.
"As one would expect, most companies fall between these two extremes in that compliance strategies may have been developed but are not yet fully executed," said CPTC's Mr. Neumann.
Still, companies can't simply test themselves into compliance, Eurofins' Mr. Navarro noted. "Testing is just one facet-one way of verification-that any quality system should have. You're going to need vendor verification programs, traceability checks, documentation, internal auditing and auditing from third parties."
Mr. Jaksch of ChromaDex said GMPs represent a motivating factor intent on furthering better business practices and assuring quality products. "Personally, I wish the industry had done this on its own volition without the FDA," he said. "That didn't happen, so it's good to see there is some motivating factor driving people to improve the quality of their products. The groundwork has been laid; now it's just a matter of companies stepping up and actually doing the testing they need."
How enactment and enforcement of these regulations will impact the industry moving forward depends on several factors. But ultimately, many believe the companies that fail to offer an effective quality assurance program will be pushed out of the market entirely.
"Just as we have seen in the pharmaceutical industry, the testing of quality into products will eventually yield to a more proactive 'quality by design' approach whereby the emphasis shifts to 'up front' quality assurance activities such as vendor qualification, supply chain quality management, science-based product development, and the validation of critical manufacturing processes," said Mr. Neumann.
Mr. Jaksch predicted the nutraceuticals industry would undergo a transformation similar to that of generic and over-the-counter (OTC) drug manufacturers in the late 1980s and early 1990s, when stakeholders saw significant consolidation of market share into a handful of larger companies.
In the end, "if an entrepreneur can't establish quality, safety and consistency, then I don't know that they should be playing the game anyway," said USP's Mr. Griffiths.
In light of several recent high profile cases, such as the Hydroxycut recall, the spiking of protein with melamine, and the peanut butter/salmonella scare that led to massive product recalls, quality and safety have become critical factors in the maturation of the nutraceuticals market.
"You can't measure quality without testing," said Ed Wyszumiala, general manager, Dietary Supplements, Functional Foods and Athletic Banned Substances Certification Programs, NSF International, Ann Arbor, MI. "The demand for safer, quality dietary supplement products among consumers and athletes, combined with new FDA guidelines, have raised the bar for the manufacturing and production of supplements. As a result, purity testing has been a top priority for dietary supplement and ingredient manufacturers that are committed to communicating the integrity of their products."
Testing will continue to be an important and ever-present part of doing business, according to William Neumann, vice president, Quality & Regulatory Affairs, Consumer Product Testing Co., Inc. (CPTC), Fairfield, NJ. "Good nutraceutical companies perform sufficient testing to assure that quality requirements are met at all stages up and down the supply chain."
Quality assurance requires several levels of testing, Mr. Neumann said, including "physical testing (e.g., tablet hardness, weight variation of dosage units, disintegration and dissolution); analytical testing (e.g., assay of active ingredients and chemical impurities); and microbial testing (e.g., bacterial count and the presence of pathogens)."
"Such testing utilizes a wide range of techniques and methodologies and is typically performed on incoming raw materials, in-process batch samples, finished product batch samples, validation samples and stability samples," he added.
Ways and Means
Raw material identification is the first and most important test in satisfying GMPs for quality control, according to Elan Sudberg, lab manager, Alkemists Pharmaceuticals, Costa Mesa CA. "It makes no sense testing for anything before confirming the identity of an ingredient."
Common and accepted identification methods include organoleptic analysis, microscopy, infrared (IR) technology, high performance liquid chromatography (HPLC) and/or gas chromatography (GC).
"Due to the highly complicated matrix and variability of botanical extracts and raw material in the marketplace, an extensive library of reference materials and methods is crucial to reliably identify such material with any of these techniques," said Mr. Sudberg.
Experts often point to the importance of validating analytical test methods, but interestingly, Frank Jaksch, president and CEO, ChromaDex, Irvine, CA, noted that GMPs don't call for compendial or validated standards. "The rule is very specific and calls for 'scientifically valid' methods. It means they want to see you're using some rationale for choosing the best method."
However, Mr. Sudberg said that as an analytical lab, Alkemists receives specification sheets accompanying dietary supplements stating certain levels of constituents without noting methodology to reflect the source of data. "It is very difficult to extract methodology from companies overseas or even on this continent due to the mysterious proprietary methods of manufacturers," he said. "If specs are to be confirmed, it would help to have the methodology used by the ingredient manufacturer for third party verification."
Mr. Jaksch used stevia as an example of the variance among similar products in the market. "There are guys out there selling 97%, 98% and even 99% stevia," he noted. "Well, what does that really mean? How did you get that number? Depending on the method you use you can get a significant variance of numbers. And companies will use that to basically play games."
Carlos Navarro, marketing manager, Eurofins Scientific, Metairie, LA, agreed that efforts to standardize methods should be a point of focus. "There are so many methods out there it requires a great amount of diligence to have things validated," he said.
While GMPs don't call specifically for compendial standards, they do stipulate that companies must conduct identity testing on every lot of every raw material, said Darryl Sullivan, associate director, Scientific Affairs & Analytical Services, Covance Laboratories, Madison, WI. "I see a lot of people trying to do some sort of 'quick and dirty' identification testing. We need some better validation around those test methods and we probably need to put some more rigor around that."
James Griffiths, vice president, Food, Dietary Supplement & Excipient Standards, U.S. Pharmacopeia (USP), Rockville, MD, agreed that more companies should invest energy and ideas into how they can effectively authenticate their materials. "Maybe it's a mixture of two or three analyzers in tandem, each of which use a more simplified method, but together give a high level of confidence that my stuff is my stuff," he said.
Among many other challenges in the testing arena, laboratories must also find low-level contaminants that originate from the environment, manufacturing process or storage containers. "This includes primary pollutants, residual solvents, agrochemicals, veterinary drugs and chemical species found in 'plastic' containers," said CPTC's Mr. Neumann. "The sensitivity and accuracy that such testing requires is resulting in an increased dependence upon mass spectrometry."
Adulterant Du Jour
Especially in an age where intentional, economically motivated adulteration jeopardizes the health and safety of consumers, as well as the overall credibility of the industry, those in the testing arena need to be more proactive, according to USP's Mr. Griffiths. "We're going to run ourselves ragged looking for the next melamine, because the bad guys are always going to be one step ahead," he said. "Let's have a protein analyzer, not a melamine analyzer. Acetaminophen, bilberry, sucrose-all these things need to be addressable from the authenticated substance, not the adulterant du jour. You're going to bankrupt yourself or drive yourself crazy trying to always be reactive in this environment."
Mr. Sullivan of Covance agreed that adulteration demands attention. "What sort of preventive testing can we do to guard against the next adulterant? We need to be able to respond to something that comes along, validate those test methods and produce data quickly. In my laboratory world that's one of the big challenges we face."
As consumers continue to seek out less costly products given current economic conditions, "the time will remain ripe for the bad guys to swoop in and skim something off before the next crisis and then move on," Mr. Griffiths added.
Such activity also leaves credible companies operating under best practices vulnerable to guilt by association. "I think the last couple of food scandals illustrated the point that if there is one bad player the whole segment suffers," said Markus Lipp, director of food standards with USP.
Mr. Navarro of Eurofins also said there has been a greater push toward ensuring food safety. "More companies are starting to think about it, whether they're doing it in house or subbing it out to testing companies," he noted.
In order to stand apart from those who don't hold the best interest of consumers in mind, NSF's Mr. Wyszumiala said, "It's important that companies have their ingredients tested and certified by an accredited, independent, third-party organization such as NSF, as well as have their facility GMP registered."
Given the attention paid to recent cases, consumers have also become very conscious of quality issues in today's marketplace, said Mr. Sudberg, of Alkemists Pharmaceuticals. "Over the last three to four years numerous product recalls and contamination issues have empowered consumers to be more informed of what level of quality assurance/control to expect from a product."
For example, label claim verification has become another critical component of nutraceutical testing, as independent watchdogs like ConsumerLab.com continue to evaluate and publish results about finished products. "In terms of verifying label claims, GMPs are clear that is going to be a major requisite," said Mr. Navarro.
Start Your Engines
So, given increased focus on testing, are companies prepared to comply with GMP requirements? And how will regulation impact the industry landscape?
Most experts seem to agree that while larger companies-many of which have modeled their operations after pharmaceutical companies-have prepared themselves for GMP compliance, others have done very little.
"As one would expect, most companies fall between these two extremes in that compliance strategies may have been developed but are not yet fully executed," said CPTC's Mr. Neumann.
Still, companies can't simply test themselves into compliance, Eurofins' Mr. Navarro noted. "Testing is just one facet-one way of verification-that any quality system should have. You're going to need vendor verification programs, traceability checks, documentation, internal auditing and auditing from third parties."
Mr. Jaksch of ChromaDex said GMPs represent a motivating factor intent on furthering better business practices and assuring quality products. "Personally, I wish the industry had done this on its own volition without the FDA," he said. "That didn't happen, so it's good to see there is some motivating factor driving people to improve the quality of their products. The groundwork has been laid; now it's just a matter of companies stepping up and actually doing the testing they need."
How enactment and enforcement of these regulations will impact the industry moving forward depends on several factors. But ultimately, many believe the companies that fail to offer an effective quality assurance program will be pushed out of the market entirely.
"Just as we have seen in the pharmaceutical industry, the testing of quality into products will eventually yield to a more proactive 'quality by design' approach whereby the emphasis shifts to 'up front' quality assurance activities such as vendor qualification, supply chain quality management, science-based product development, and the validation of critical manufacturing processes," said Mr. Neumann.
Mr. Jaksch predicted the nutraceuticals industry would undergo a transformation similar to that of generic and over-the-counter (OTC) drug manufacturers in the late 1980s and early 1990s, when stakeholders saw significant consolidation of market share into a handful of larger companies.
In the end, "if an entrepreneur can't establish quality, safety and consistency, then I don't know that they should be playing the game anyway," said USP's Mr. Griffiths.
