Ben Locwin, Contributing Editor03.09.16
While people take supplements for a variety of reasons, ensuring quality, consistency, and potency are the principal themes the nutritional supplement industry can control so that consumers know that they are getting what they pay for.
Do you currently take a nutritional supplement? This can be anything aside from food and prescription medicine that you take to augment your nutritional status—whether it be a vitamin/mineral supplement, healthy fats, herbal supplements and plant extracts, probiotics, etc. Most people do in fact take nutritional supplements, and it is an industry averaging over $37 billion currently, with $5.7 billion in sales just from multivitamin/mineral supplements alone.1
Oversight of a dynamic industry
The good news is that the manufacture and quality control of nutritional supplements has markedly improved over the past several years. Supplement manufacturers who are looking to have their branding listed at professional sports events and other public locations typically become less risk-tolerant the more exposure they get. And it makes sense: If a new marketing campaign costs $30 million, the added exposure and boost to sales brings with it the potential for increased market profile for regulatory scrutiny or greater numbers of consumer-reported complaints or negative social media buzz.
So who’s taking them? Given the diversity of the nutritional supplement industry, stratifying who is taking what sort of supplement can be done in any number of ways. At least in terms of the most general form of nutritional supplement—a multivitamin/mineral supplement, evidence shows that use is more frequent among females; the children of women who use supplements; the elderly; those with higher education; higher socioeconomic status; and lower body-mass indexes (BMI).2 This is a very broad, and in some cases very vulnerable, cross-section of the population, and so safety of nutritional supplements has a tangible impact on communities.
In part because of the increased scrutiny on professional sports for the screening of performance-enhancing drugs (PEDs), supplement manufacturers have worked to distance themselves from the past perceptions of an industry without controls. Just a decade ago, there were more supplements identified by rate which either were found to have banned substances in them, active pharmaceutical ingredients, or dosing problems. What seemed to be an industry out of control is one that has largely been taking the message from the public very seriously and improving their internal standards. There are now many more nutritional supplements, which are certified GMP for Sport, NSF certified (NSF/ANSI 173), QAI, or other labels to show the level of diligence being undertaken during the manufacturing processes. But while the FDA is not authorized to review dietary supplement products for safety and effectiveness before they are marketed, they can inspect firms for their adherence to cGMPs. So what do the current data show?
About 71%—444 out of 626—of the dietary supplement manufacturers inspected by FDA for cGMPs received a Form 483, in which the Agency cited the manufacturers with an average of 7 observations each. These observations stemmed from any number of causes, including lack of facility sanitation, missing or inadequate documentation in the form of process batch records, improper verification of ingredients, inadequate monitoring of potency, and so forth.
About one-third of manufacturing firms received a status of Official Action Indicated (OAI), which is FDA parlance for a status that “occurs when significant objectionable conditions or practices were found and regulatory action is warranted to address the establishment’s lack of compliance with statute(s) or regulation(s).”1
In addition, about one-third of firms received a Voluntary Action Indicated (VAI) status which is indicative of a condition that “occurs when objectionable conditions or practices were found that do not meet the threshold of regulatory significance.”3
The remaining proportion, slightly under one-third, were inspections in which FDA sought ‘no action.’
Part of the proportion of total findings stems from the fact that the FDA is requiring dietary supplement manufacturers to comply with cGMPs for dietary supplements, and not for cGMPs for food, which is a regulatory shift for improvement that occurred a several years ago; effective September 2007 with a 3-year phase-in to allow for industry-wide compliance. This is important, because unlike food, consumers are trusting that the tablet, capsule, or powder is what it says it is when it often can’t be discerned visually.
Here is a brief primer on the FDA’s regulation of dietary supplements (21 CFR Part 111):
Though the number of adverse events stemming from dietary supplements has steadily increased over the past seven years (see Figure 1), these data are not normalized for proportion of consumers taking supplements, nor for the different supplements on the market, so the interpretation needs a bit of caution.
More people taking more different types of supplements will undoubtedly lead to an increase in post-market reports of consumer adverse events. Not all supplements work for everyone, nor do they work for each person in the same way; there are genetic factors, which tend to produce pharmacogenomic clusters in the population, epigenetic factors, and independent lifestyle factors. And additionally, the more the public becomes aware of adverse event reports the more they will be behaviorally primed and apt to document their personal cases.
This shouldn’t be taken as a negative result. Surely if there are supplements or ingredients on the market, which seem to be contributing to a disproportionately-high level of adverse events, then they should be further examined to protect the public health and well-being. In addition, simply looking at the number of Form 483s issued by FDA does little to tell a story of how good or bad the nutritional supplement industry is; if anyone is telling you that it does, they are wrong. Some are minor and some are major findings, but taken as a whole they represent how the industry is evolving forward to maintain regulatory compliance. As we collect more data from the consumer market, and as more firms increase their compliance with cGMPs, the industry will continue to move in a positive direction.
References and Further Reading
Ben Locwin
Contributing Editor
Ben Locwin is an author of a wide variety of scientific articles for books and magazines, as well as an acclaimed speaker. He is an expert media contact for the American Association of Pharmaceutical Scientists (AAPS) and a committee member for the American Statistical Association (ASA). He also provides advisement to many organizations and boards for a range of business, healthcare, clinical, and patient concerns. He can be reached at ben.locwin@healthcarescienceadvisors.com.
Do you currently take a nutritional supplement? This can be anything aside from food and prescription medicine that you take to augment your nutritional status—whether it be a vitamin/mineral supplement, healthy fats, herbal supplements and plant extracts, probiotics, etc. Most people do in fact take nutritional supplements, and it is an industry averaging over $37 billion currently, with $5.7 billion in sales just from multivitamin/mineral supplements alone.1
Oversight of a dynamic industry
The good news is that the manufacture and quality control of nutritional supplements has markedly improved over the past several years. Supplement manufacturers who are looking to have their branding listed at professional sports events and other public locations typically become less risk-tolerant the more exposure they get. And it makes sense: If a new marketing campaign costs $30 million, the added exposure and boost to sales brings with it the potential for increased market profile for regulatory scrutiny or greater numbers of consumer-reported complaints or negative social media buzz.
So who’s taking them? Given the diversity of the nutritional supplement industry, stratifying who is taking what sort of supplement can be done in any number of ways. At least in terms of the most general form of nutritional supplement—a multivitamin/mineral supplement, evidence shows that use is more frequent among females; the children of women who use supplements; the elderly; those with higher education; higher socioeconomic status; and lower body-mass indexes (BMI).2 This is a very broad, and in some cases very vulnerable, cross-section of the population, and so safety of nutritional supplements has a tangible impact on communities.
In part because of the increased scrutiny on professional sports for the screening of performance-enhancing drugs (PEDs), supplement manufacturers have worked to distance themselves from the past perceptions of an industry without controls. Just a decade ago, there were more supplements identified by rate which either were found to have banned substances in them, active pharmaceutical ingredients, or dosing problems. What seemed to be an industry out of control is one that has largely been taking the message from the public very seriously and improving their internal standards. There are now many more nutritional supplements, which are certified GMP for Sport, NSF certified (NSF/ANSI 173), QAI, or other labels to show the level of diligence being undertaken during the manufacturing processes. But while the FDA is not authorized to review dietary supplement products for safety and effectiveness before they are marketed, they can inspect firms for their adherence to cGMPs. So what do the current data show?
About 71%—444 out of 626—of the dietary supplement manufacturers inspected by FDA for cGMPs received a Form 483, in which the Agency cited the manufacturers with an average of 7 observations each. These observations stemmed from any number of causes, including lack of facility sanitation, missing or inadequate documentation in the form of process batch records, improper verification of ingredients, inadequate monitoring of potency, and so forth.
About one-third of manufacturing firms received a status of Official Action Indicated (OAI), which is FDA parlance for a status that “occurs when significant objectionable conditions or practices were found and regulatory action is warranted to address the establishment’s lack of compliance with statute(s) or regulation(s).”1
In addition, about one-third of firms received a Voluntary Action Indicated (VAI) status which is indicative of a condition that “occurs when objectionable conditions or practices were found that do not meet the threshold of regulatory significance.”3
The remaining proportion, slightly under one-third, were inspections in which FDA sought ‘no action.’
Part of the proportion of total findings stems from the fact that the FDA is requiring dietary supplement manufacturers to comply with cGMPs for dietary supplements, and not for cGMPs for food, which is a regulatory shift for improvement that occurred a several years ago; effective September 2007 with a 3-year phase-in to allow for industry-wide compliance. This is important, because unlike food, consumers are trusting that the tablet, capsule, or powder is what it says it is when it often can’t be discerned visually.
Here is a brief primer on the FDA’s regulation of dietary supplements (21 CFR Part 111):
- Marketing claims: They make sure dietary supplement companies do not claim their products prevent, treat, or cure diseases.
- New ingredients: The FDA reviews and approves the introduction of new ingredients to the market by affirming generally recognized as safe (GRAS) status, or as new dietary ingredients (NDI).
- Safety: If evidence indicates an ingredient is harmful, the FDA establishes supplement label warning requirements or will mandate removal of an ingredient from the market.
- Chemistry, Manufacturing, and Controls (CMC): The FDA inspects manufacturing facilities to make sure they follow current Good Manufacturing Practices (cGMPs), which includes verification of raw materials, production practices, and finished product analytical testing.
Though the number of adverse events stemming from dietary supplements has steadily increased over the past seven years (see Figure 1), these data are not normalized for proportion of consumers taking supplements, nor for the different supplements on the market, so the interpretation needs a bit of caution.
More people taking more different types of supplements will undoubtedly lead to an increase in post-market reports of consumer adverse events. Not all supplements work for everyone, nor do they work for each person in the same way; there are genetic factors, which tend to produce pharmacogenomic clusters in the population, epigenetic factors, and independent lifestyle factors. And additionally, the more the public becomes aware of adverse event reports the more they will be behaviorally primed and apt to document their personal cases.
This shouldn’t be taken as a negative result. Surely if there are supplements or ingredients on the market, which seem to be contributing to a disproportionately-high level of adverse events, then they should be further examined to protect the public health and well-being. In addition, simply looking at the number of Form 483s issued by FDA does little to tell a story of how good or bad the nutritional supplement industry is; if anyone is telling you that it does, they are wrong. Some are minor and some are major findings, but taken as a whole they represent how the industry is evolving forward to maintain regulatory compliance. As we collect more data from the consumer market, and as more firms increase their compliance with cGMPs, the industry will continue to move in a positive direction.
References and Further Reading
- Nutrition Business Journal. NBJ's Supplement Business Report 2015. Penton Media, Inc., 2015.
- NIH State-of-the-Science Panel. (2007). National Institutes of Health state-of-the-science conference statement: multivitamin/mineral supplements and chronic disease prevention. American Journal of Clinical Nutrition,85:257S-264S.
- FDA, (2012). Public Disclosure. About FDA – Transparency. http://www.fda.gov/downloads/AboutFDA/Transparency/PublicDisclosure/GlossaryofAcronymsandAbbreviations/UCM212061.pdf
Ben Locwin
Contributing Editor
Ben Locwin is an author of a wide variety of scientific articles for books and magazines, as well as an acclaimed speaker. He is an expert media contact for the American Association of Pharmaceutical Scientists (AAPS) and a committee member for the American Statistical Association (ASA). He also provides advisement to many organizations and boards for a range of business, healthcare, clinical, and patient concerns. He can be reached at ben.locwin@healthcarescienceadvisors.com.