Manufacturers

Finished product testing requirements puts pressure on multiple ingredient products, expert says

16-Dec-2013 - By Hank Schultz
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Setting specifications for products and testing to make sure the lots going out the door meet those specs is a key facet of meeting GMP requirements.  But if a company has a product that might include many ingredients, how does it formulate a realistic testing regimen to make sure all of those ingredients are there in their specified amounts? Good question, said an expert.

James Neal Kababick, director of Flora Research Laboratories in Grants Pass, OR, spoke with NutraIngredients-USA about the challenge presented by multiple-ingredient products. In the initial phase of GMP inspections, FDA has repeatedly cited firms for failure to product specifications that comply with the regulations.  Going along with that is the failure of many firms to conduct compliant finished product tests.

Kitchen sink on steroids

Complicating the picture is the habit by formulators in some product categories to include as many ingredients as will fit on the label in an effort to differentiate their products from those of their competitors.  This seems especially true in the sports nutrition sphere where the kitchen sink approach goes on steroids and ingredient lists plump up accordingly.  One pre workout product examined recently lists more than 50 active ingredients on the label.  How would a company realistically (and cost effectively) ensure that all of those ingredients were consistently showing up at their specified levels in the finished product?

“It would a costly process, and depending on the ingredients and their levels, it may require in-process testing,” Neal-Kababick said.

Multiple ingredient strategy

In the products that contain such a plethora of ingredients, it’s highly unlikely that all of them are present in efficacious dosages, Neal-Kababick said.  But product formulators might have another goal in mind, to make it difficult for competitors to duplicate the mix.

“It’s a little bit of a red herring thing in that it creates a little bit more difficult time to duplicate the product,” he said. “A competitor would spend a lot of money doing the analysis. A deformulation test on a complex blend like [the one mentioned above] might easily cost $100,000.”

Deconstructing the blend

James Neal-Kababick, Director of Flora Research Laboratories

One approach a company might take with such a complicated formula would be to test select component streams of the product, Neal-Kababick said.  For example,  a company could show that sub portions  A through E of its multiple-ingredient proprietary blend were meeting spec at the time of their inclusions into manufacturing process for the finished product. The company could also devise a finished product testing strategy that looked at, say, five major constituents of the finished product to verify that these were within parameters.  If all of that data matched up, it could be reasonable to conclude that the finished product, in toto, met its specification, he said.

But that still wouldn’t get a company off the hook for making sure that a specification exists for all of those ingredients, and that the finished product matches that spec.  As FDA starts in on the second round of GMP inspections, the agency has been delving more deeply into the testing aspect, moving from making sure firms are doing testing in the first place for identity and quality, to whether the tests companies are using are fit for purpose and whether those tests are showing the results they should. Even if precise levels of ingredients in a proprietary blend are not called out on the product label, a master manufacturing record should list these levels (assuming it complies with GMP requirements.) FDA could take a company to task if some of the lower dose constituents are out of spec, or if they are not there at all, Neal-Kababick said.

“FDA might start saying that in your energy complex propriety blend your MMR [master manufacturing record] says you have 15 mg of creatine, but when we tested the surveillance samples we only found 5,” Neal-Kababick said. “That’s what’s going to be an issue in those cases.  They still have the charge to meet their specifications. I don’t know how you would do that without doing some chemical analysis.”

Streamlined products in the future

The net resuts of FDA’s intensified look at testing could be that bloated ingredient lists could become a thing of the past, Neal Kababick said.  This is especially true as regards the widespread use of contract manufacturers.  FDA has made it abundantly clear the brand holder owns 100 percent of the ultimate responsibility for  GMP compliance, and that includes that that 15 mg creatine (or what have you) is in the finished product.

“Companies will start to rethink whether they want to still include low level ingredients if they find that they can’t support the claim that they have that ingredient,” he said. “FDA’s point of view is that the GMPs are the GMPs. If you don’t like the cost of what it takes to do the job right then don’t do it.  They are not really concerned that you might need to buy an $800,000 instrument to do this testing.”

Related topics: Regulation, Manufacturers, Proteins, peptides, amino acids, Sports nutrition