It's one of the great mysteries vexing the natural products industry today: Why are European and American regulators so skeptical about the health benefits of probiotics? And what can the industry do to turn the tide?
Global Industry Analysts predicts that the global probiotics market will reach $29 billion in revenue by 2015, but whether that projection becomes reality may hinge on the world's regulatory authorities.
To date, European Food Safety Authority's NDA Panel has assessed – and delivered a crushing defeat – to more than 300 dossiers seeking health claims approval for probiotics. Not one product has passed the panel. And many industry insiders fear that this isn't likely to change anytime soon.
Looking to make strategic business decisions, or deciding the best form and format, with a probiotic product? Get the Ingredient Intelligence Monograph.
Meanwhile, in the United States, regulators are presenting similar obstacles. In the past few years, the Federal Trade Commission has challenged the advertising claims of several probiotic products, the most famous being the December 2010 settlement with Dannon Co. for its yogurt product Activia.
The company agreed to stop claiming that single daily serving of Activia relieves irregularity (it would take three servings of Activia to reach the appropriate probiotics dosage level), or that its DanActive yogurt drink helps people avoid catching colds or the flu. The company also had to fork over $21 million in a related class action lawsuit over these claims, which had been brought about by various state Attorney Generals.
With more than 5,700 papers and clinical trials published on probiotics in peer-reviewed literature, probiotics manufacturers are understandably vexed. Why do regulators seem to be so willing to go against the scientific grain when it comes to probiotics?
CRN's Duffy MacKay speaks on probiotics
NewHope360 sat down recently with Duffy MacKay, the Council for Responsible Nutrition's vice president of science and regulatory affairs, to try to get some answers:
NH360: In a nutshell, what is going on here? Why is it so difficult to come up with a health claim -- or a marketing message -- that regulators are okay with?
DM:In the U.S., there are no approved health claims or qualified health claims for probiotics. So, for example, you cannot say in an ad or a product label that a probiotic "shortens the duration of a cold." What we are left with, then, are structure-function claims -- things like "helps maintain healthy microintestinal flora" or "helps maintain a healthy gut." The FDA isn't going to challenge something like that because it is general enough with good science to support it, and those claims are used a lot.
But here is the problem: How do you support structure-function claims with clinical studies scientifically? No one has defined what a "healthy gut" looks like. What are the clinical end points? If you are trying to design a study to really validate that claim, how do you know if you have gotten there yet?
It's much easier to design a study that shows that a certain strain reduces constipation or diarrhea, but those are clinical end points, which are not permitted in a food product. Clinical end points take you out of the world of food, and into the drug category.
NH360: But clinical end points like a reduction in diarrhea, or shortening the duration of a cold, is precisely the kind of information that would be most beneficial to consumers. That's what I want to know as a consumer – not something vague like "helps maintain a healthy gut." Does this mean no one can do a study like that?
DM:Probiotics developers can and do perform studies with clinical endpoints, and it is extremely time consuming and expensive to do. And once you have your results, you can't use them in any of your advertising or project packaging because it suggests the intended use is as a drug
Because probiotics are bugs – living organisms – if you design a study using clinical end points, it is considered a drug study. So you have to fill out an Investigational New Drug (IND) application, which goes to the Center for Biologics Evaluation and Research (CBER). And the CBER is going to use the same criteria to evaluate the probiotic as they would a live vaccine.
Here we have dozens of probiotics, from a variety of strains widely known to be consumed safely, and if you want to do a study on diarrhea in children, you must go to the CBER and provide exhaustive technical information on the products, just to get the study under way. It is proving to be an enormous challenge to researchers.
Structure function claims
NH360: So in other words, you can do a structure-function claim like "maintains healthy gut," but because there are no defined clinical endpoints for a healthy gut, designing this type of study is complex. Or you can do a study with specific end points, like measuring cold duration, but then you have a drug study, not a food study, and probiotics cannot claim drug-like results.
DM:Exactly. CRN has submitted comments to the FDA on the topic of requirements related to designing clinical studies for dietary supplements and used the example of probiotics to illustrate just how complex this issue is, and how regulatory guidelines are proving to be a real barrier to research. Regulatory linguistics is really driving where science is able to go.
NH360: So what's the solution?
DM:Two things. One, we need validated biomarkers for structure-function claims. The scientific community needs to define what a "healthy gut" means, and then the FDA will ultimately decide if they are valid or not. Such an effort is in the nascent stages right now, with groups like the International Probiotics Association. And two, we need to reconcile (regulations concerning) INDs for probiotics. Holding them to the same standard as a vaccine doesn't make sense. A different set of criteria should be used.
NH360: In the meantime, how do product formulators get the word out about the research they do conduct?
DM:Companies can't say that a product helps reduce colds and flu, even if they have research showing it, so they have to reach consumers another way: editorials, third-party literature. It would be really good for mothers to know that if they consume certain strains of probiotics in their pregnancy, that it might help prevent eczema or allergies in their child – but under the current system, it's very difficult for them to find this out. This just shows that it isn't only probiotics manufacturers who are being hurt. At the end of the day, its consumers who are hurt the most.
Want to learn more? Ingredient Intelligence Monograph takes an in-depth look at the latest market developments, regulatory trends, and how to get there now in the probiotics world.