FDA cGMP project - labels and language

Though not technically part of the regulations that govern good manufacturing practices, product labels, websites, and social media pages and the language they contain are also regulated by FDA and are, unfortunately, a ripe potential target for government agents who enjoy browsing the internet at their desks. Lately, warning letters have been issued just for unapproved website claims (for example, here). Regardless, it makes good sense to start by having compliant packaging and marketing materials: anything else invites scrutiny.


**NOTE: all the information presented under the "FDA cGMP compliance open source project" is not intended to be legal advice, nor is it in any way guaranteed that my interpretation of the statute and system for compliance is going to satisfy any individual FDA inspector or compliance officer. These pages are a synthesis of my own understanding of the regulations and how to achieve compliance.

We'll look at the label itself in a bit. First, what about claims on labels? There are two types: ingredient claims (this much Vitamin C, for instance, or these many calories), and structure/function claims ("supports healthy immunity" and other such language). It's rare that herbalists will need to make nutrient claims - but I've included a label for a product that contains some honey, so you can see how to articulate the carbohydrate count on a label. But structure/function claims are a source of perpetual befuddlement. What can be said? What cannot? Are there code phrases or tricks?

I will start by saying that there really aren't tricks. You can't get away with saying "this statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease" and then making any claim you want. You can't say "traditionally used" in front of any claim you want, and think this exempts the language. You can't get tricky and say things like "useful during the cold and flu season", because colds and flus are diseases, and herbs can't be useful during disease season because "useful" can only mean "medically useful" in this context. You can make a claim that a supplement supports the normal, healthy function of an organ, system, process or function of the physiology, provided those processes and functions are part of the normal, healthy course of life. You can also use language that FDA doesn't understand, or considers meaningless - like "enhancing yin" or "unblocking stagnant liver qi".

This is the tricky part. It really is up to FDA to decide what a normal, healthy course of life looks like and I have to say that, based on my experience, it appears FDA (and/or their medical consultant squad) spends a little too much time sitting at desks on the computer, eating a questionable diet, feeling stressed and not sleeping too well. This is in part because anxiety, tension and stress, occasional heartburn, gas, upset stomach, PMS and insomnia are all considered part of a normal, healthy course of life. But I digress.
Blood-based parameters - like blood sugar, cholesterol, pressure etc... - are fair game as long as it is clear that the herbal product "supports healthy blood sugar levels that are already in a normal range" (emphasis mine, and is required). Anything else would imply disrupted blood levels, which means disease. Certainly can't mention diabetes.
I have found the following document very helpful:
http://www.fda.gov/ohrms/dockets/98fr/010600a.txt
It gives a good background on how we got here (namely, the Dietary Supplement Health and Education Act, or DSHEA), which is interesting to read if you like context. But you can also search the document right in your web browser. Try typing in "heartburn". Or "blood pressure". Or "insomnia". Then, try "potency" (improving sexual potency is not an acceptable claim, but improving sexual performance is - poor performance is apparently part of a normal, healthy course of life).
These searches give you ways to approach herbal actions from an acceptable structure-function perspective, and more importantly, if you spend a little time reading, you can get a good sense of what will be acceptable, and what might get you into trouble. There are some tricks - "occasional" heartburn and sleeplessness are fine, but without that qualifier, they are diseases (though of course this wouldn't work for "occasional" migraines). Best of all, FDA explicitly says "this is acceptable" after a good many statements, and you can use these statements as you see fit. Beyond this, you have to prove that a claim refers to supporting something that happens anyway as part of being a healthy human if you want to use it.
All claims - even mentioning the word "immune" in a product name - must have an asterisk next to them. This asterisk must point to the FDA disclaimer somewhere on your label, which must be enclosed in a hairline box: "These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease."

These regulations around claims apply to print and internet material, too. Brochures, business cards, shelf talkers and sales sheets, catalogs, websites, and social media pages - even, perhaps, audio and video - must all comply (and must include the FDA disclaimer). You can't control what others post on your sites - but don't "like" or acknowledge them. Testimonials, if not properly worded, aren't acceptable either. Personally, this is a big loss: I remember back in the day herb companies often had some of the best information on herbs, their pharmacology and applications, in their print and web media. Now, you can't even post a study that references one of the herbs you use because it's seen as implying that the herb can actually do what it does in the study.
One way around this is to set up, or ally yourself with, a few personal social media pages and weblogs. You can link to these from your product pages, even if these external sites say outlandish unacceptable things like how herbs prevent heart attacks. Some warn that such sites must be "two links" away from your herbal company's website - I haven't seen this distinction in action yet.

Once you have defined what acceptable claims you want to use (and I do recommend connecting with ahpa.org to find a lawyer to review these, if you have the financial means), you are required to submit them to FDA, just to let them know that you're saying herbs do things, within 30 days of beginning sales of the product. Here's an example of what such a letter might look like, including the address to send it to:

Herb Pharm Liquid Herbal Extract Vein Health Letter.

Furthermore, you are required to have files that substantiate the claims you're making: if, for example, your elderberry syrup says it supports the immune system, you should have a file that references actual research and dosing, and/or traditional sources (such as 19th century texts), pointing to elderberry's effectiveness (you just can't ever share any of that information with the public on your website).

How to build such claim substantiation files? In the near future, I'd love to start sharing some of what we've put together and would welcome anyone else's support in this. Perhaps a shared online repository? To a certain extent, some of the files are customized for a particular formula or extraction - but there is still the possibility for substantial overlap. For now, start at Health Canada (in many ways more enlightened on this particular regulatory topic), where monographs on many plants are included with references that back up a range of claims. Note, however, that most of these claims are unacceptable to FDA - such as Ashwagandha's effect as a sleep aid - but you can rephrase it as "helps with occasional sleeplessness" and use the Health Canada reference as part of your claim substantiation.

http://webprod.hc-sc.gc.ca/nhpid-bdipsn/monosReq.do?lang=eng&monotype=single


Now, we can look at the specifics of label regulations themselves. There are rules for how a food label generally, and a dietary supplement label specifically, must be structured. There are also variations in requirements depending on the label size. And there is a specific exemption: if there are no nutrient claims or structure/function claims on the label, and there are no wholesale sales, and total annual sales are less than $500,000 or there are less than 100,000 units of a product sold, then having a supplement facts label is not required. If you want to sell your products through a store or distributor, this exemption is not an option. It really only applies to herb shops, farmer's markets, and direct-to-consumer sales.
General rules on food labeling, including the details on exemptions (found in subsection (j)) are in the Code of Federal Regulations (CFR), Title 21, Part 101, subpart 9 (abbreviated as 21CFR101.9). Find the whole thing here:
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=101.9
Specific rules on dietary supplement labeling are in 21CFR101.36, which is available here:
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=101.36
I'll go over these regulations while looking at some specific label examples, which makes it much more clear. But a few pieces to note:
- less that 12 square inches on a label allows you to use 4.5 point font. Anything bigger than 40 square inches requires 6 point at a minimum for text, and 8 point at a minimum for the serving size text in the supplements facts box.
- note the requirements for hairlines, lines, and columns in the supplements facts box. There are some good examples included in 21CFR101.36
- list plants by common name and include the part (root, rhizome, leaf, seed, flower, etc...)
- many herb supplements only need a proprietary blend listed, along with a symbol pointing to a footnote that says "% Daily Value not established". If you add honey or other sweeteners, you may need to list the carbohydrates/sugars, and perhaps the calories, per serving (if the amount per serving exceeds 1g of carbohydrates, and/or if it exceeds 5 calories). The website nutritiondata.com gives good carb/sugars counts for various foods (and a whole lot of other stuff, here's an example for honey: http://nutritiondata.self.com/facts/sweets/5568/2). Just remember, if your serving is 2ml, and there's less than 1g of carbohydrates in there, you don't have to list them on the supplements facts panel.

So, with a little of the background information available, let's take a look at some example labels for two different sizes of a dietary supplement that also contains a little honey. Because writing it all out would take too long, here is a voice walk-through identifying all the important pieces of a (in this case liquid) herbal dietary supplement:

And here are the labels: first, a larger size with a complete supplements facts panel.


Next, a small size with a "linear" supplement facts declaration (only for labels smaller than 12 square inches, though you could make a case to use this way if it's under 40 square inches and there's no room for a big panel).





Next week we'll start to talk about the ingredients and packaging that go into making dietary supplements: from herbs and other ingredients, to your labels, bottles, closures and seals. We'll look at specifications and hopefully get to some ideas on testing. Another piece to cover (if we can get to it) is getting to know your vendors and "qualifying" them to help streamline future work. As always, questions and comments are welcome and I will do my best to include your experience in the conversation. Anyone who has had labels vetted by FDA inspection or legal counsel is really encouraged to send examples to guido at urbanmoonshine dot com. Thank you!