FTIR and FDA Warning Letters
By Elan Sudberg
One of the hardest things I have ever done in my life was to earn a degree in chemistry. While I claimed three other majors before that and could have graduated so many years earlier, I knew I had to understand the foundations of phyto/fungal chemicals to be good at measuring them later for all my favorite brands. School was never easy for me and combined with my choice in degree, while simultaneously starting Alkemist Labs with my father, I ended up spending a lot of office hours with my chemistry professors, trying not to fail. I always made it known I was working and running a natural product testing lab after school hoping they’d take some sort of nostalgic pity on me, but they did not.
We started the Alkemist Labs with two time tested and globally accepted ~rudimentary techniques for botanical and fungi identity: light microscopy and high-performance thin layer chromatography (HPTLC). If there was an award for re-pioneering oldie but goodie testing technology, we should have earned it by now. Meanwhile the peddlers of a new tricorder promising to be “the lab in a box the botanical world has all been waiting for” began their marketing campaign of ‘trust us’ and ‘we rely on a proprietary reference library for which, so sorry, you can’t audit.’ Oh, and those algorithms (facepalm). It was/still is called FTIR and if you sense a negative stance on its use in our industry, you are correct. Keep reading.
While Fourier-transform infrared spectroscopy (FTIR), a technique where an infrared spectrum of light is used to measure absorption or emission of a solid, liquid, or gas, has been around and widely accepted as an important analytical instrument for almost 60 years, its primary strength was for structural elucidation of single molecules. That’s ‘nerdish’ for identifying a simple chemical.
Back to those office hours… It is still not uncommon for Alkemist to fail a botanical/fungus by HPTLC that passed by FTIR. At one point early in my college and Alkemist career, I had a collection of FTIR C of As from other labs (mostly unknown ones in the back of an ingredient supplier’s warehouse) and often shared them with my advanced organic chemistry professor, Dr. Lopez and analytical chemistry professor, Dr. Anjo. They were flabbergasted as to how such tech as FTIR could be used to confirm identification of a plant/fungus. The issue was and still is that plants are complicated mixtures of hundreds of fine chemicals and most of those are beneath the surface trapped in cells or extracted out in specific fractions. Those professors helped me coin the phrase ‘Fit for Purpose’ as applied to testing techniques good and bad. I spoke around the country on this topic for years. My stance then and now is that FTIR is not fit for purpose to identify and differentiate plant species or complicated mixtures of plant products.
To be clear, FTIR has the potential to be used appropriately IF ones spends the time and money to create a robust reference library. Unfortunately the logical fallacy of ‘willful ignorance’ where one refuses to change one’s mind or consider conflicting information based on a desire to maintain one’s existing beliefs is at play and perpetuated by the ‘poisonous complacent shoulder shrug’.
Still, thanks to ambiguously written cGMPs which require only that you toss some science at the sample before you sell it (I am being a little facetious) and NOT a specific method to use or NOT use, some in this industry (you know who you are and so I do I…) still use it. And invariably when fit for purpose testing is applied to that same material, we have to fail their samples.
Why am I bringing this up? I swear it’s not because I am tired of fighting for fit for purpose methodologies. I love that fight. I eat that fight every morning like it’s organic chia seed pudding. It’s because it’s been really hard not to yell out loud, “Told You So!!!! “as I devour the weekly FDA warning letters and wade knee deep through the constant calling out of misused FTIR to identify botanicals in raw and finished goods.
What’s happening? The FDA has finally dug in at a deeper than normal level on the question, ‘how do you know this is working?’ It’s only been six months, yet the writing on the wall already says “you should have listened to Elan.” Excerpts from just a few of the FDA warning letters issued, and quoted below, show a trend:
“There is no assurance that your FTIR methodology provides the requisite specificity and that it is scientifically valid for identifying botanicals.”
“FTIR could not identify the individual dietary ingredients within the blend. While FTIR may be used to verify that the supplier is consistent in sending the same component, FTIR does not ensure that the component received is what it is claimed to be when the component is a blend with multiple ingredients.”
“Specifically, the FTIR analysis performed by your third-party laboratory uses previous shipments of components as the reference for testing and they do not own a reference library for the FTIR tests. Testing components against previous shipments of the component may confirm receipt of the same component but this does not ensure the identity, purity, quality, and strength of the component is thoroughly characterized .”
“Identity testing using FTIR to compare the sample spectrum to an unverified reference sample is not an appropriate, scientifically valid method to verify that specifications are met.”
This tale of woe ends, like all the others I have written through the years, with the best advice I have to offer: check those labs. External or internal, labs are fallible and there is a way to check yourself before you reck yourself by doing a little detective work.
Click on: https://datadashboard.fda.gov/ora/index.htm and see if that contract manufacturer or lab has a good record of keeping clear of logical fallacies. And remember kids -fit for purpose testing is the only way to go.