21 CFR 114 (acidified foods) applies to Dietary Supplements?

First I'd like to say hello, this is my first time posting in the Forum.  I found IFSQN recently and was excited to have done so.  What a great resource and community.

 

To give you a quick back ground, I own and operate a DS firm (Dietary supplement manufacturing), regulated by 21 CFR 111.  We have recently started filling cold fill liquids, mainly items like 5 hour energy shots, L-Carnitine supplements, etc.  

 

After a recent FDA inspection they issued us a 483 for not complying with the Acidified food regs, and not registering as a FCE or form 2541 and for not filing form 2541e for acidified foods and Process Authority. 

 

After speaking to several PA's (Process Authority) I found that all came to a similar conclusion, that DS are not regulated by 21 CFR 114; however, I think it's really more a case that FDA has never enforced these regs on DS firms. More than likely FSMA is part of what is driving this push.  

 

So lets just agree that no one wants to get into a fight over CFR interpretation with the FDA, so we will just assume that the over arching Food regs cover everything DS unless otherwise exempted.  

 

So now that brings me to another item, the products the FDA observed do not meet the definition of an Acidified food in my opinion as well as the opinion of the Process Authority we did seek out.  Before any acidulants were added our True Avg pH was around 4.53.  Now anyone can see that 4.53 is getting close to the upper limit of Acid  or Low Acid and because of this we feel it's best to still follow through with a Voluntary submittal of form 2541e, as well as follow through with having a PA fully evaluate the product, despite the fact that these regs are definitely a bit antiquated when it comes to items like energy shots. 

 

In order to complete a PA we need to have a Challenge Study performed and this is actually the area I am having most of my issues. I have contacted 3 micro labs so far and not a single one has a good idea on how to put together a challenge study protocol for a product that is similar to a 5 hour energy.  Now how can this be?  I am a little bit floored that labs that employee micro biologist and whose sole purpose is to understand micros and know how to properly test, can't figure how the best way to set up a study for a product of this nature.

 

So this is the main question I am left with and looking for help, suggestions on how to set up a proper Challenge Study for a dietary supplement that is high acid and using your typical preservative combination, Sodium benzoate and sorbic acid, However, if anyone has anything to say or comment on any of the other specifics to this long post I'd love to hear your thoughts.

 

Thanks again for your time and thoughts and I look forward to actively participating in this community.

 

Best,

 

Jess

 

 

The first thing that comes to my mind is testing pH of your product(s) post production over weeks/months so ensure that your equilibrium pH never rises above 4.6 (though most would suggest you should try and keep it below 4.5) As your product is shelf stable, that will ultimately be the FDAs concern.

 

If your product hermetically sealed and/or pasteurized?

 

It's a bit concerning when you say your true average pH was 4.53.........did any go over 4.6?  Are your preservatives enough to prevent botulism?

I would agree with FDA that it should be treated as an AF.

 

The issue is the cold fill. FDA's concern would be that since your product isn't pasteurized it may have organisms that would raise pH and allow C. bot to grow. I've worked with Covance before, they had the necessary expertise and process authorities on staff to help you design a study and submit. You will likely need to include preservatives to prevent yeast/mold growth if you do not pasteurize.

It's a bit concerning when you say your true average pH was 4.53.........did any go over 4.6? Are your preservatives enough to prevent botulism?

The final pH of the product is much lower, around 3.7. We add additional acid and of course preservatives, the main point I’m making to FDA with the pH range under 4.6 is that it doesn’t meet the definition of an acidified food or a low acid food prior to adding acidifying agents.

Carbonated beverages, jams, jellies, preserves, acid foods (including such foods as standardized and nonstandardized food dressings and condiment sauces) that contain small amounts of low-acid food(s) and have a resultant finished equilibrium pH that does not significantly differ from that of the predominant acid or acid food, and foods that are stored, distributed, and retailed under refrigeration are excluded from the coverage of this part.

 

A point of part 114 is that it says it applies to "foods", which in the FDCA includes 

 

 

I think it depends on the formulation ultimately, I'm confused as to how this is an acid food since your ingredients before you add acidulants are basically purified water, sugar, flavors, and vitamins/caffeine, correct? Presumably then if the material is mostly water and not a naturally acidic liquid (like fruit juice), your pH is very variable based on the pH of the incoming water or exposure to the air. Further, you stated that your AVERAGE pH was 4.53, what's the standard deviation? what percentage of product would be over 4.6?

 

Basically, because you have decided to acidify this product, as you said, to create a margin of safety, you've identified it as a low acid food, otherwise you wouldn't bother acidifying it. By doing it you've defined it.

 

The (now withdrawn) fda guidance still used at the state level provides some additional definitions that are helpful here:

 

“Acid food containing small amounts of low-acid food(s)” - We use this term to refer to an acid food that is excluded from the coverage of 21 CFR part 114 because it contains small amounts of low-acid food(s) and has a resultant finished equilibrium pH that does not significantly differ from that of the predominant acid or acid food.

 

 

 

Your product's final pH DOES significantly differ. The further define in the guidance what a "significant shift" in pH is:

 

If the equilibrium pH of the predominant acid or acid food is:>4.2

Then you should consider a shift in pH to be significant when: Any shift in pH is present

 

 

Ergo you don't have an acid food or an "acid food containing small amounts of low-acid foods", because the resultant finished equilibrium pH significantly differs from that of the predominant acid or acid food.

 

You also probably fall under the "water based liquids" definition in the guidance, which specifically states that non-juice products like yours when acids are added to bring pH below 4.6 are considered acidified foods.

 

And yes, while it's "guidance" (and withdrawn guidance at that) you can bet that FDA still treats it as law.