There is no dispute that cannabis is a complex plant often used as a botanical drug, food, food ingredient, and textile. With no federal oversight, regulatory bodies of the now 29 United States and the District of Columbia where cannabis is legal in some form, are tasked with ensuring product safety to their constituents. Most states require finished product testing by the International Organization for Standardization and the International Electrotechnical Commission (ISO/IEC) 17025 accredited laboratories. Laboratory accreditation to ISO/IEC 17025 represents a laboratory’s commitment to develop protocols to ensure quality practices are implemented and includes the attestation of their competence by an independent third party. Whenever possible or when mandated, analytical labs rely on published consensus and standard test methods or to validate their modifications to such methods to perform the necessary work. Although standard methods are in development by scientific organizations such as AOAC International and ASTM, as of this writing there is not a single published compendial or consensus method for the most typical assays used in the cannabis industry. This article discusses basic principles of quality assurance and laboratory accreditation, and the current status of voluntary methods in development. A final intent of this article is to provide unique insight into the challenges associated with testing cannabis amidst the federal prohibition.
Many of the states that require cannabis-product testing by third-party laboratories also require that laboratories be accredited to ISO/IEC 17025 by a recognized accreditation body (AB). ISO/IEC 17025 is the pinnacle international standard of accreditation for laboratory quality and technical competence. The accreditation process relies on a uniform approach of technical assessment, shown to increase confidence in data through traceability and reproducibility (36). Accreditation bodies are themselves accredited to ISO/IEC 17011 and subject to peer evaluations in the cooperative. Popular ABs for the United States cannabis industry are the American Association for Laboratory Accreditation (A2LA), ANSI-ASQ National Accreditation Board (ANAB), and Perry Johnson Laboratory Accreditation (PJLA). The fundamental difference between a certification program such as ISO/IEC 9001 and ISO/IEC 17025 is that 17025 accreditation is the determination of technical competence to perform specified methods by an independent and impartial third party, whereas ISO/IEC 9001 certification means a laboratory has a quality management system. Governments and regulatory bodies worldwide have embraced ISO/IEC 17025 as a means to establish confidence that the laboratory product (derived data) is quality driven.
Standard and Consensus Test Methods: What Is the Difference?
Prescribed practices, including analytical laboratory test methods, can be developed by any person, laboratory, or organization and may be promoted as “standard practices.” Before implementing a standard of any sort, however, users should thoroughly investigate and appraise the basis of the standard practice and also evaluate the history and credibility of the person or organization that developed the standard. In terms of standard analytical test methods, once a method is published in a scientific journal, it may be adopted by any laboratory and referenced as a published method. The term consensus methods, however, refers to methods that have undergone an extensive peer-review process, through which participants have reached consensus on the utility and specification of a given method. Typically, as consensus methods become preferred or required by a governing body, they are referenced as “standard methods.”
One of the more technical requirements of ISO/IEC 17025 is the application of analytical methods that are scientifically sound. Most often, laboratories will choose standard or consensus test methods that have been peer-reviewed where major performance parameters including measurement uncertainty have been specified. Laboratories adopting these standard methods must demonstrate the ability to properly implement the methods before introducing actual test samples. On occasion, a laboratory may choose to modify an existing standard method. In this case, the laboratory must demonstrate equivalency of the modified method to the standard method. This process is referred to as method verification. In the absence of standard methods, laboratories are compelled to develop and validate their own methods. ISO/IEC 8402 defines method validation as “the confirmation by examination and provision of objective evidence that the particular requirements for a specific intended use are fulfilled” (27). AOAC International, ASTM, and the American Chemical Society (ACS) have published guidelines for single laboratory method validation. In general, method validation studies must demonstrate statistically sound performance with respect to precision, accuracy, specificity, linearity, selectivity, detection limit, limit of quantitation, and so on, and must also include measurements of uncertainty (28,29).
Currently, there are no standard test methods available for dried cannabis flower or any other cannabis matrix. Several scientific organizations have embraced stakeholder needs and are actively developing standard methods: AOAC International, American Oil Chemist Society (AOCS), ASTM International, and the US Pharmacopeia (USP). Each of these institutions carries a long and rich service history of developing standards as elements to the provision of consumer safety. The AOAC was initially formed under the US Department of Agriculture in 1884 as the Association of Agricultural Chemists, and through the years became an independent and international organization encompassing all branches of science that affect (predominantly) the food and feed industries. Many of the voluntary methods approved by the AOAC’s Official Method Board are recognized as industry standards by the FDA and other regulatory bodies (27). Similarly, ASTM International was established in 1898 to address stakeholder needs for standard specifications for materials. Since its inception, ASTM formed many communities designed to identify and address their specific needs. Although developed methods are intended to be available for voluntary use by stakeholders, they often become recognized as industry standards (31). Formed as the Society of Cotton Products Analysts 1909, the AOCS has been providing voluntary methods for the oil and fat communities (32). Finally, the USP was established in 1820 to provide a formulary of medicines to ensure public safety. Over the years, they have developed standards for food ingredients, medicines, and dietary supplements (33). As with the other organizations, the USP is not a regulatory body, but their standards are enforceable by the FDA.
In 2016, the AOAC International formed a Cannabis Advisory Panel and Cannabis Working Group. They have since developed several standard method performance requirements (SMPRs) for analytical methods, and an Expert Review Panel is currently evaluating candidate methods. In 2017 the ASTM formed Cannabis Division, D37, that has identified subcommittees to address the broad spectrum of stakeholder needs such as personnel, cultivation, laboratory testing, process and handling, and security and transportation. Also in 2017, D37 hosted a cannabis and hemp workshop in Berlin to engage with European stakeholders. The AOCS has also embraced the opportunity and are working with stakeholders to develop standard test methods. Establishing and vetting these methods is neither easy nor quick; however, each organization is diligently at work. Once established, most consensus or standard test methods endure for decades because of their sound and solid scientific foundations.
- M. Booth, Cannabis: A History (St. Martin’s Press, New York, 2005).
- E. Russo, H.E. Jiang, X. Li, A. Sutton, A. Carboni, F. del Bianco, G. Mandolino, D.J. Potter, Y. Zhao, S. Bera, Y. Zhang, E. Lu, D.K. Ferguson, F. Hueber, L. Zhao, C. Liu, Y. Wang, and C. Li, J. Exp. Bot. 59(15), 4171-4182 (2008).
- L.L. Iversen, The Science of Marijuana (Oxford University Press, New York, 2008).
- E.B. Russo, in Handbook of Cannabis, R.G. Pertwee, Ed. (Oxford University Press, New York, 2014), pp. 23-43.
- V. Angelova, R. Ivanova, V. Delibaltova, and K. Ivanov, Industrial Crops and Products 19(3), 197-205 (2004).
- S. Mukherjee, The Public Domain Review, Retrieved January 15, 2018 from https://publicdomainreview.org/2017/04/19.
- US Pharmacopeia, 3rd Edition. Retrieved January 15, 2018, from http:antiquecannabisbook.com/view.timeline.php.
- D.F. Musto, Scientific American 20-27 (July 1991). Retrieved from https://faculty.unlv.edu.
- Federal Food and Drugs Act of 1906 (The “Wiley Act”), Public Law Number 59-384, 34 STAT.768 (1906), 21 USC Sec 1-15 (1934). Retrieved from www.fda.gov/regulatoryinformation/lawsenforcedbyFDA/ucm148690.
- H.R. 18583, 91st Congress of the United States (1970).
- United States Drug Enforcement Administration. Drug Scheduling. Retrieved from www.dea.gov/druginfo/ds.
- National Academies of Sciences, Engineering, and Medicine, The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research (The National Academies of Press, Washington, DC, 2017). Doi:10.17226/24625.
- V. DiMarzo, D. Melck, T. Bisogno, and L. De Petrocellis, Trends in Neurosciences 21, 521-528 (1998).
- J.M. Cole, Deputy Attorney General. Memorandum for all United States Attorneys (August 29, 2013). Retrieved January 10, 2018 from www.mpp.org/federal/cole-memo.
- B.T. Yeh, The Controlled Substances Act: Regulatory Requirements (2012). Retrieved January 15, 2018 from https://fas.org/sgp/crc/mis.
- Federal Drug Administration Food Safety Modernization Act of 2011. Retrieved January 15, 2018 from https://www.fda.gov/food/guidanceregulations/fsma.
- US Food and Drug Administration, Good Laboratory Practices. Retrieved January 30, 2018: www.fda-glp.com (FDA, Rockville, Maryland).
- US Food and Drug Administration, Facts about Current Good Manufacturing Practices. Retrieved January 30, 2018: www.fda.gov/drugs/development/approvalprocess/manufacturing (FDA, Rockville, Maryland).
- International Conference on Harmonization, Harmonised Tripartite Guideline, Guideline for Good Clinical Practice, E6(R1) (ICH, Geneva, Switzerland, 1996).
- US Food and Drug Administration, FDA and Marijuana: Questions and Answers. Retrieved January 30, 2018: www.fda.gov/newsevents/publichealthfocus (FDA, Rockville, Maryland).
- H.R. 2642, 130th Congress of the United States, 2nd Session (2014).
- M.A. ElSohly, and D. Slade, Life Sciences 78, 539-548 (2005).
- G.A. Cabral, E.S. Raborn, and G.A. Ferreira, “Phytocannabinoids and the Immune System,” in Handbook of Cannabis, R.G. Pertwee, Ed. (Oxford University Press, New York, 2014), pp. 261-274.
- U. Pagotto, G. Marsicano, D. Cota, B. Lutz, and R. Pasquali, Endocrine Reviews 27(1), 73-100 (2006).
- M.A. ElSohly, in Emerging Issues in Analytical Chemistry, B.F. Thomas, Ed. (Elsevier, Amsterdam, The Netherlands, 2016).
- A. Thompson and V. Langfield, in Handbook of Cannabis, R.G. Pertwee, Ed. (Oxford University Press, New York, 2014), pp. 356-372.
- M. Backes, Cannabis Pharmacy (Black Dog & Leventhal Publishers, New York, 2014).
- M. Starks, Marijuana Chemistry (Ronin Publishing, Inc., Berkeley, California, 1990).
- A. Hazecamp, A. Peltenburg, R. Verpoorte, and C. Giroud, Journal of Liquid Chromatography & Related Technologies 28, 2361-2382 (2005).
- International Laboratory Accreditation Cooperation (ILAC). Retrieved January 20, 2018 from www.ILAC.gov.
- International Organization for Standardization. (1994). Quality management and quality assurance - vocabulary (ISO Standard No. 8402).
- E. Pritchard and V. Barwick, Quality Assurance in Analytical Chemistry (Wiley Publishers, West Sussex, UK, 2007).
- M.E. Swartz and I.S. Krull, Handbook of Analytical Validation (CRC Press, Boca Raton, Florida, 2012).
- AOAC International. Retrieved January 29, 2018: www.aoac.org/aoac_prod_imis/APAC/AB/AOAC.
- ASTM International, The History of ASTM International. Retrieved January 29, 2018: www.astm.org/about/history_book.
- American Oil Chemists’ Society, History of AOCS. Retrieved January 29, 2018: www.aocs.org/info/about-aocs/history-of-aocs.
- US Pharmacopeia, Our History. Retrieved January 29, 2018: www.usp.org/about.
How to Cite This Article
S. Audino, Cannabis Science and Technology 1(1), 14-20 (2018).