Thursday, August 8, 2019
Why are all the cannabis regulatory labs failing?
Some people know that I've been doing some weird stuff in 2019, largely due to a huge number of mass spectrometry labs that have opened and suffered catastrophic failures in the last 3 years here in North America. A couple of people contacted me with this idea, light years ahead of a new entire multi- BILLION dollar industry with this crazy idea "what if...hear me out...what if... we opened a mass spectometry company and ...yes...I know this is crazy.... we got the advice of someone who had actually operated a mass spectrometer before?!? Told, you, crazy."
What I've found in the last 7 months or so is an industry right on the edge of catastrophic collapse, where ignorance and bravado and the huge margins of the industry combine to put consumers continuously at risk. The following text is part of a larger article I'm preparing for an industry journal. I'll be honest. I think Cannabis is stupid. If there is anything I find more annoying than Cannabis culture, it is having a conversation with someone who is cognitively impaired by it during said conversation. However, I firmly believe that an adult person should be allowed to do what they want if it doesn't harm others and that they have a right to their own safety, particularly if they're purchasing a commercial product in the land of corporate greed. Even if you are a fan of the atrocities that are/were FISH or the Grateful dead, I don't wish you harm and if the state is hiring companies to protect you from inhaling lead and fluorinated pesticides when you purchase products (presumably to dull the awful sounds of this "music") then the people who are charged with protecting you from these risks should be doing it correctly.
The draft of this part of the article starts here:
Here in the U.S. cannabis products are exploding in popularity. Every month another state government seems to allow more use of products that contain THC, despite the continued existence of federal regulations against it. Recently, the feds have lightened up as well, with the passage of the hemp act which allows plants that don't produce THC (or levels below pharmacological relevance) to be grown and their products used.
Due to a total lack of federal oversight, the states are on their own to determine what cannabis products are legal and safe. Almost universally, all states are turning to private companies to certify that cannabis products are:
1) What they say they are (concentrations of THC and other cannabinoids and various other terpene compounds)
2) Do not contain damaging amounts of heavy metals, pesticides, solvents, and pathogenic microbes.
Nearly all of these tests are performed by analytical chemistry techniques. GC, GC-MS, HPLC, LC-MS, ICP-MS, etc.,. These are accurate, well-characterized, rapid and robust assays. And, to be honest, given the power and sophistication of today's instruments -- what the states are asking for isn't all that hard.
In order to sell a cannabis product, a private and state licensed lab must approve that batch of product for release. A single cannabis plant produces a lot of material, rapidly, and a single plant may be worth hundreds or thousands or dollars. Therefore, these rapid and easy assays are the only thing standing between someone with a greenhouse making zero or a LOT of money and this reflects in the price for each individual test. I did a quick Google search and it seems like $700 per sample is the going rate in California. How much time does it take for an LCMS run that can resolve 70+ pesticides on today's instruments at 10ppB limits of quantification? About 30 minutes, if you aren't in a hurry.
Here is the question, though: Why are the labs failing at such a remarkable rate? Here are two recent articles describing this phenomena:
Article about Oregon from February
Here's one about California
There are validated mass spectrometry assays that have hit low ppB levels on hundreds of pesticides in a single shot.
Today's ICP-MS systems can easily and rapidly hit ppTRILLION levels in heavy metal detection. Heck, here is an article from 1994.
I can go on and on. It's a great time, from an instrumentation standpoint, to be a scientist, particularly in chemisty!
I typically write on a proteomics blog where most of my audience is reliably quantifying tens of thousands, hundreds of thousands of molecules by LC-MS reproducibly each and every day. Here is a self -serving study I was lucky enough to be a part of, where my collaborators continuously quantify tens of thousands of peptides and never miss measurements, and haven't for YEARS. 72 pesticides? 40 terpenes? 20 residual solvents? With the potential to realistically bring in over $1M in revenue per month? When I first saw these figures it seemed like there HAD to be some kind of catch. Could I do this in my sleep and bring in more revenue than proteomics labs with 5x more instrumentation? Impossibly, the answer seems to be a yes. I could name, off the top of my head (with a lot of spelling mistakes) at least 100 people, many of whom I'm lucky enough to consider my friends, who could do this EASILY.
How is it possible that these labs would fail? I have a hypothesis or two, but let's look at some of the data first. I'll start with Indeed.com, a pretty large job board in the U.S. First off, let's look at what these high profit labs are paying for their Analytical Chemists.
Just for perspective, are these inexpensive places for chemists to live?
Van Nuys isn't quite as expensive. The same site tells me that the median home price is only 3 times the price of...my...home I purchased 4 years ago....
I didn't just pick through Indeed for salaries, feel free to do it yourself.
For more perspective, the thing that I think equates probably the closest to the cannabis assays I've described is probably Clinical Chemistry. Similar, though less varied, technologies in the assays and a superior focus on producing the most reproducible data. Again, I'm not trying to cherry pick data, just taking the first two I found listed side-by-side.
CLS pay is pretty rigorously detailed geographically. When you have that level of training and standardization, if another hospital pays better it's easy to move over. These are CLS I positions, typically entry level. There are certifications that must be renewed each year, but I've never heard of an employer that didn't pay those fees and when I was one I was allowed to study and take my tests on the job. CLS II is achieved after a few years of experience and accompanied by well-controlled salary increases. That's a lot of words for -- these are entry level positions that require the same basic skills.
Ummm...okay....so...let's not jump to any conclusions. A young chemist right out of school who, I dunno, maybe has a phobia to human blood or likes the constant smell of hemp material I find so unpleasant should be just as good at this stuff as anyone else, right?
In 2017, the Association of Biomedical Research Facilities (ABRF) Workflow Interest Network (WIN) set up a global mass spectrometry study (full disclaimer, I am now part of this volunteer group. I was not before, and asked to join because I was impressed by this study)...
You can download an overview of this study here.
The study went something like this:
ANY lab in the world could write in and get a complex unknown mass spectrometry sample sent to them and be part of this global study. All they had to do was run this sample and send their anonymous results and some details about themselves, their lab and their methods back to the WIN group.
52 labs wrote in.
When the initial results were presented, the ONLY variable that correlated with the quality of the results if different operators were using similar instruments was the number of years of experience the operator had actually running instruments.
I participated in this one. I had over 10 years of experience at the time. There was a high outlier (also in the green section) who obliterated the curve. Someone was much better than me, and everyone else who participated. There will be variability like that. There are some students out there who just took to mass spectrometry like a Boston Terrier to water and are probably as good or better than I am now, even though I've been doing this stuff for a living (and as my primary hobby) going on 15 years. Would I have laughed at the ease of what the Canadian government wants for a cannabis compliance lab when I was in grad school? Nope. Part of that is the hardware, most of it is software, but a lot of it is the fact that I once wrote up a panel with 900 timed targets for a new at-that-time instrument so 72 doesn't seem like that bad of a weekend.
However, it stands to reason that the two things are linked somehow. I suspect that the people setting up these high profit labs assume that this stuff is easy. I also assume the vendors don't help instill the importance with sales pitches like, "don't worry, if you go with our overpriced instruments, you'll get great data even if you go rescue 7 Rottweilers, put bologna on the keyboards and just lock the doors."
The truth of the matter is that mass spectrometry is still not easy. Does this seem contradictory because I said I could think of 100 people who could run a lab like this easily? This is a perspective issue. I got married a few years ago. We eloped to a remote location and had a party to celebrate it after the fact. I invited one person outside of my immediate family that wasn't involved in mass spectrometry to this event. Further perspective, I have a cartoon of the first (muro)glycopeptide solved entirely by tandem mass spectrometry tattooed up the length of my upper arm (Orsburn et al., 2006) and a useful equation for identifying modified mass spectrometry ions tattooed up the full length of my leg so that I would always have it if I needed it. I'm not writing this paragraph so the editor will remove it. I'm writing this because it's true and those 100 people I can think of are of a special sort of people -- focused and possibly borderline obsessed by a field of science that is very very new. How many people exist outside of this group that I'd trust could do this? World wide? A few.
When the margins are this high, does spending the money to recruit the best talent seem all that important? Guess it depends on how you look at it? Are you coming in to get through those first couple of months necessary to break even, and then each day you escape (while possibly endangering patients) before the state shuts you down, you "earn" more than your IRA will compound this year? If so, don't worry about making the effort to recruit top tier talent, I guess. I believe that this is the strategy, right now, more often than not.
The real victims here are the customers/patients using these products. The people using these products who assume that they're safe because the state they live in requires testing. The people who believe that this makes the product they just purchased and paid taxes on intrinsically safer than they would get on the street corner from a black market supplier.
I'll leave you with a local story here that illustrates this point. Recently, medical cannabis patients became more ill when using their state licensed medical products. Employees of the farm producing the materials they used came forward and described the use of illegal pesticides on these products. For fun, I downloaded all of the testing records for every batch of product produced by that farm and looked for the compounds of interest (publicly available). Despite levels of these compounds high enough to make people ill, there is no record that this farm ever failed a test on a product batch that was released to a dispensary for sale.
I haven't been in this industry long, and honestly, I don't expect to stay. I saw a chance to make an impact in a field that desperately needs help and is directly affecting millions of people, who are potentially exposed to harm. I've spend months developing SOPs, protocols and methods papers, many of which are in preparation or in stages of review to try and make an impact for as long as I can. What I've found in this time is that there are many good companies that believe in their products and, whether misplaced or not, believe that these products can and will help patients. I've also observed just as many, if not more, bad actors who are only in the Cannabis market to make a quick $1M (or...more accurately... $100M..) and who consider the users of these products little more than criminals who deserve the effects of whatever corners they cut before they cash out their shares.
Will Cannabis regulatory labs continue to fail? Absolutely. Honestly, as the states get better at regulating, I expect -- and hope -- they'll fail at a faster rate than ever. I've seen too much bad science, bad data, and bad actors and too much improvement in the government agencies in the 3 states I interact with to think anything else. This latter part is what I'm most optimistic about. The government agencies I work with are increasingly sophisticated and knowledgeable and fully aware of the short comings of the market they are charged with regulating.
What is the solution? A simple paradigm shift. The first company led by mass spectrometrists who hire their sales, marketing and financial people, rather than the current system that is the opposite, will dominate this market and ultimately push out their competition. The resulting labs will easily stand up to the improvements in government scrutiny as the rest fail due to inexperience or general inadequacy. Will this happen soon? I sure hope so.