Inter-Lab Variation in the Cannabis Industry, Part I: Problem and Causes

April 4, 2019
Volume: 
2
Issue: 
2
Abstract / Synopsis: 

Too often, cannabis laboratories get different results on the same sample. There are a number of causes and solutions. In this installment, the problem is presented along with its causes. In the second part of this series, potential solutions will be discussed.

In the first installment of this column series, I stated one of my goals was to teach the basics of chemical analysis for those in the cannabis industry that are new to the field (1). I started by writing columns on precision and accuracy (2) and representative sampling (3). Normally at this point in a course on analytical chemistry I would proceed onto a topic such as the basics of chromatography. However, one of my other goals for this column is to address important issues facing the cannabis analysis industry. There now exists an issue so important in this industry that I feel the need to interrupt your regularly scheduled cannabis analysis column for this important message: inter-laboratory variation is a serious problem in our industry. I feel it is so important that I will be devoting this and the next column to this topic.

 

Cannabis is Medicine…Test it Like Medicine!

The U.S. Food and Drug Administration (FDA) is now on record stating that cannabidiol (CBD) has medicinal uses (4). Here is an excerpt from their announcement: “Marketing unapproved products, with uncertain dosages and formulations can keep patients from accessing appropriate, recognized therapies to treat serious and even fatal diseases.” Thus, the FDA has set itself the goal of insuring cannabis medicines contain correct dosages.

One of my mantras is, “Cannabis is medicine . . . test it like medicine!” (This phrase was in the running to be the name of this column series, but I thought “Cannabis Analysis” was easier to say and remember.) The point is that the cannabis industry needs to adopt the testing regimen of the pharmaceutical industry to produce safe and effective medicines, and the FDA agrees with me. This means performing what I call cradle-to-grave testing: Analyzing raw materials for identity and purity, monitoring every step of the chemical manufacturing process to make sure it is done according to standard operating procedures; testing final products for correct amounts of active pharmaceutical ingredients (APIs) and excipients; and testing for compliance with any applicable laws and regulations. Many cannabis businesses are dependent upon third party cannabis analysis laboratories for some or all their testing.

Inter-laboratory variation is the problem of different laboratories obtaining statistically different results on the same sample. It is a well documented phenomenon in the cannabis industry (5–8). One of the best papers on this topic is surprisingly found in the pages of the prestigious Journal of the American Medical Association (JAMA) (5). The authors purchased 84 CBD containing products over the internet from 31 different companies, and had their potencies analyzed by an independent laboratory. More than 69% of these products were mislabeled. One of the likely explanations for this problem is inter-laboratory variation—the laboratories who analyzed these products for label claims incorrectly measured the amount of CBD in the samples. Based on this study, it sounds like the FDA has its work cut out for it trying to insure cannabis patients get the right dosage of CBD.

In addition to the JAMA article, local news teams have been on the hunt investigating inter-laboratory variation in the cannabis industry (6,7). In one study (7), the same homogenized cannabis oil sample was delivered by hand to 10 different cannabis testing laboratories in California. The range of measured potencies was from 64% to 83%. There is no other explanation for these results but inter-laboratory variation. An internet search will turn up other such studies with similar results.

Some colleagues and I recently performed a round-robin study of five California cannabis laboratories (8). We took a sample of distillate known to be free of pesticides, spiked it with known amounts of six different pesticides, and hand delivered the samples in duplicate to the laboratories on the same day. The false negative rate was 78%. That is, 78% of the time the laboratories failed to detect pesticides known to be present in the distillate. Our results probably mean pesticide tainted products have made it into the hands of California cannabis patients and consumers.

Additionally, we submitted homogenized distillate samples from the same batch in quadruplicate to the five different laboratories (8). The range of the 20 potency measurements received was 77% to 94%. Again, the cause here must be inter-laboratory variation. We proved via mid-infrared (IR) spectroscopy that the sample was homogeneous (8). I am sure many of you have heard of or experienced the inter-laboratory variation problem yourselves.

Let’s review the results here:

  1. 69% of CBD products mislabeled with the wrong dosage.
  2. Measured potency range of 64% to 83% measured on the same sample by 10 laboratories.
  3. Pesticide false negative rate of 78%.
  4. Measured potency range of 77% to 94% measured on same sample by five laboratories.

These results are shocking and unacceptable. Can you imagine the uproar if 69% of a company’s pills sold to the public were found to have the wrong amount of API? Can you imagine the controversy that would result if we found out that 78% of the food we eat contained previously undetected pesticides? There would be reams of bad press, a raft of lawsuits, congressional investigations, companies going bankrupt, and maybe even people going to jail. This will happen to our industry if we don’t fix the inter-laboratory variation problem.

References: 
  1. B.C. Smith, Cannabis Science and Technology 1(3), 10–12 (2018).
  2. B.C. Smith, Cannabis Science and Technology 1(4), 12–16 (2018).
  3. B.C. Smith, Cannabis Science and Technology 2(1), 14–19 (2019).
  4. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm611046.htm.
  5. M.O. Bonn-Miller, M.J.E. Loflin, B.F. Thomas, J.P. Marcu, T. Hyke, and V. Ryan, Journal of the American Medical Association 318, 1708 (2017).
  6. B. Young, The Seattle Times, January 5, 2016. https://www.seattletimes.com/seattle-news/marijuana/some-pot-labs-in-state-failed-no-pot-at-all-says-scientist/.
  7. https://www.nbcbayarea.com/investigations/Industry-Insiders-Warn-of-Fraud-at-Marijuana-Testing-Labs-458125743.html?_osource=SocialFlowFB_BAYBrand.
  8. B.C. Smith, P. Lessard, and R. Pearson, Cannabis Science and Technology 2(1), 48–53 (2019).
  9. https://www.nist.gov/publications/development-and-certification-green-tea-containing-standard-reference-materials.
  10. A. Hazekamp, A. Peltenburg, R. Verpoorte, and C. Giroud, J. Liquid Chrom. & Related Techniques 28, 2361 (2005).
  11. B. De Backer, B. Debrus, P. Lebrun, L. Theunis, N. Dubois, L. Decock, A Verstraete, P. Hubert, and C. Charlier, J. Chromatrography B 877, 4115 (2009).
  12. M. Giese, M. Lewis, L. Giese, and K. Smith, J. AOAC Intl. 98, 1503 (2015).
  13. M. Starks, Marijuana Chemistry (Ronin Publishing, Oakland, California, 1977).
  14. J. Fairbairn, J. Liebmann, and M. Rowan, Journal of Pharmacy and Pharmcacology 28, 1 (1976).
  15. I. Trofin, G. Dabija, D. Vaireanu, and L. Filipescu, Revista de Chimie (Bucharest) 63, 293 (2012).
  16. C. Lindholst, Australian Journal of Forensic Sciences 42, 181 (2010).
  17. B.C. Smith, Terpenes & Testing Magazine, Nov./Dec.(6), 48–51 (2017).

 

Brian C. Smith, PhD, is Founder, CEO, and Chief Technical Officer of Big Sur Scientific in Capitola, California. Dr. Smith has more than 40 years of experience as an industrial analytical chemist having worked for such companies as Xerox, IBM, Waters Associates, and Princeton Instruments. For 20 years he ran Spectros Associates, an analytical chemistry training and consulting firm where he taught thousands of people around the world how to improve their chemical analyses. Dr. Smith has written three books on infrared spectroscopy, and earned his PhD in physical chemistry from Dartmouth College.

How to Cite This Article

B.C. Smith, Cannabis Science and Technology 2(2), 12-17 (2019).