Why Good Manufacturing Practices Will Play a Central Role in the Global Cannabis Industry
As the industry breaks free from the stigma associated with nearly a century of prohibition and draconian attitudes, the modern consumer now enjoys legal access to this formerly taboo plant medicine in many parts of the US and several other countries. In this new paradigm of cannabis commerce, the options are vast. The popularity of traditional smokable dried cannabis is as strong as ever, yet there are also vape pens and dab sauces galore, more varieties of edibles than Willy Wonka, Martha Stewart, and Snoop Dogg combined could have imagined – tinctures, topicals, bath bombs, soaps, suppositories and more. But what do they all have in common? Consider an often-mentioned acronym, GMP.
There’s a lot of buzz around good manufacturing practices (GMP) in the cannabis industry, or perhaps more accurately, the lack thereof. For better or for worse, cannabis exists in a unique purgatory between its illicit street-market history and full-blown regulatory oversight. As of early 2021, cannabis in the US remains a Schedule I drug “with no known medicinal purpose,” contrary to the preponderance of evidence in support of its many benefits to human health and wellness. Because of this status, federal agencies like the Food & Drug Administration (FDA) remain mostly hands-off, even though many cannabis products would fall under its umbrella of regulations as do other food, drugs, or cosmetics.
In lieu of federal oversight, state regulations govern the cultivation, production, distribution, and sale of cannabis products, aiming to ensure safety and prevent sales to minors or diversion to back-door markets. Most regulations stop short of implementing formal GMP requirements, and compliance to the rigors of these practices is not yet fully mandated. Regardless, many cannabis cultivators and manufacturers pursue a corporate culture in the spirit of GMP standards, typically owing to key players in upper management with former experience in parallel industries that conform to GMP.
What are good manufacturing practices?
GMPs were born as consumer protection laws intended to prevent poisoning or sickness from food or drugs and to prevent labeling fraud or post-packaging tampering. One particular incident in the late 1930s that led to over 100 deaths in 15 states prompted a full overhaul of previous regulations and adoption of the 1938 Food, Drug, and Cosmetic Act, which remains the basis of the FDA’s authority to regulate drugs today. By 1969, in response to ongoing risks posed by uncontrolled manufacturing processes in food and drugs, the FDA launched the initial version of GMP standards we know today, requiring detailed and documented controls in manufacturing to meet specific quality characteristics the products are purported to possess. These principles extended beyond the pharmaceutical industry – from car manufacturing, to food and cosmetics, to medical devices – all types of production rely on the concepts of systematically building quality control into processes in a stepwise manner, which documents the who, what, when, and how much of every component that affects the specifications and safety of the final product.
The principles of GMP are captured in the International Conference on Harmonization (ICH) guidelines, globally governing pharmaceutical manufacturing operations of active pharmaceutical ingredients intended for human use (Good Manufacturing Practice guide for Active Pharmaceutical Ingredients Q7). Here, manufacturing “is defined to include all operations of receipt of materials, production, packaging, repackaging, labelling, relabeling, quality control, release, storage and distribution.” All of these elements apply to cannabis. And most likely, most companies already have written policies and procedures controlling these processes due to state requirements for licensure. In the United States, the regulatory guidelines are published in the Code of Federal Regulations (CFR) Title 21 on Food and Drugs.
But the cost burden of implementing GMP principles and activities has always been a contentious issue. In reality, the up-front expenses are investments in protecting the company’s bottom line. In the cannabis industry, recalls are not taken lightly and can permanently damage a brand’s reputation. Recalls can occur as a result of scenarios GMPs are intended to prevent, such as contamination, labeling errors, or adulteration. Potency and dosage information for products containing THC need to be strictly controlled, to sustain consumer confidence and avoid undesirable end-user experiences. An accidental double-dosed edible could have significant consequences for a novice end-user. A vape pen claiming to be high-CBD/low-THC could cause unintended effects for the consumer in the case of a mislabeled unit, perhaps containing upwards of 90 percent THC instead of the stated dominance of CBD.
It’s also in the best interest of a cultivator to have confidence that once products leave the licensee’s site for distribution, there are protections in place to prevent tampering or adulteration of product within the supply chain, en route to consumer shelves. For example, it would be a shame for a brand producing top-shelf cured cannabis to realize its customers bought items that had been swapped with a product of lesser quality. All sorts of foreseeable and preventable risks to consumer safety and brand reputation can be prevented by adhering to the intentions of GMP guidelines. The good news is, in the cannabis industry the wheel need not be reinvented. Title 21 CFR, Part 111, is broadly applicable to the packaging, labeling, and storing of dietary supplements, and provides a detailed framework suitable for cannabis manufacturing.
Documentation management systems and software
Not long ago, the vast majority of documentation associated with quality management systems (QMS) was paper based. A popular mantra of quality systems management reminds us, “if it wasn’t written down, it never happened.” But electronic records have rapidly become the new normal, spurred by economical cloud-based web services providing secure storage options for businesses. Regulations have adapted in response and now include specifications for data integrity in both paper-based or electronic systems, requiring records be secured, verifiable, indelible, traceable, accurate, non-corruptible, and retrievable. While some businesses may have complex needs that require an in-house, custom-built digital storage software system, there are many offerings on the market that will suit the needs of cannabis product manufacturers.
Electronic document management systems (eDMS) are, by design, fully validated and qualified for uses conforming to the Code of Federal Regulations (CFR) Title 21 Part 11. This means in addition to the traits listed above, they are attributable, contemporaneous, backed-up, with and controlled access rights (granted during employee or other stakeholder onboarding, revoked during offboarding). In cannabis cultivation, processing, and manufacturing, all batch records should be handled in this manner to protect the good standing of the company’s license in the case of a state audit. The advantage of implementing a software-as-a-service (SaaS)-based eDMS or digital QMS platform is to centralize all the required conformance elements into a single portal with controlled access and disaster-recovery periodic archives.
Risk-based approaches to controlling processes
A risk-based approach involves identifying points in components or processes most likely to fail and putting safeguards in place to prevent failures. Levels of risk are generally determined by assessing the combination of the probability of occurrence of harm and the severity of that harm. In the food safety world, this concept is known as hazard analysis and critical control point (HACCP), a system in which the critical control points are identified, limits to specifications are implemented with continuous monitoring, and corrected action is triggered when specifications are not met. The framework outlined in Title 21 CFR Part 117 provides guidelines on records to be maintained, facility and personnel qualifications for food handling, sanitation, supply-chain programs including supplier verification, hazard analysis, risk-based preventative control measures, corrective actions, recall plans and much more.
Many of the principles established in food safety for sanitation and prevention of cross-contamination are also embraced in the cannabis industry. For example, at a cultivation site, one of the greatest risks stems from an accidental introduction of a particular pest into the crop, or worse, the mother stock. In order to mitigate this risk, steps are taken to quarantine new plants before introduction to the main facility. Immature plants are monitored in a designated, separated quarantine space for signs of disease before release into other areas. Sometimes plants are tested genetically for particularly crop-crippling pathogens before approval for release. To further prevent the spread of disease in the event plants do get sick, tools, materials and even employees are dedicated to segregated areas to prevent commingling between different stages of crop production, for example from vegetative to flowering growth periods. Protection of the mother stock may be so important that pruning shears are dedicated to only one plant, or rigorous cleaning occurs for all tools in contact with plant tissue between one plant and the next.
Using a risk-based approach, data-driven tracking of quality metrics informs decisions to create a feedback loop of continuous improvement under documented management review. Corrective and preventative action records (CAPAs) are central principles of a QMS that support the manufacturing processes and includes QA/QC testing activities – periodic checks to ensure the final product meets the specifications of safety, efficacy and consistent quality set forth for each product type. Strict control is applied over all labeling activities, and safeguards are in place to prevent accidental mix-ups of product.
Personnel and training
GMP guidelines surrounding personnel are largely focused on documentation, a central hallmark of GMP standards. Employees’ qualifications must meet the job description for the position for which they were hired and require the employee signature to affirm and acknowledge the stated duties. A formal onboarding process is well-documented and applied to all new employees. Training also follows a prescribed program, often involving a three-phased process where the employee observes a qualified individual perform tasks, then performs those tasks under supervision, before being qualified to perform the tasks on their own. All training activities are captured in the employee’s training files, and demonstrations of competency are recorded initially and renewed at least annually. A master training matrix is housed in the quality system which contains a list of all tasks necessary during production, and which personnel are authorized to perform them. Offboarding is a formal process as well, ensuring the newly separated individual’s access privileges to facilities and computer systems are revoked and the employee file is archived.
All industries experience turnover, and a primary goal is to minimize any impact to operations and product quality as the staff changes. Formalized standard operating procedures (SOPs) are therefore central to the training process and to maintaining consistent product quality. Whenever activities deviate from the current SOPs, documentation must occur to capture the differences in protocol in order to provide details that may prove beneficial in the event of products found to be “out-of-specification” (OOS) downstream. Corrective actions and/or preventative actions (CAPA) may be launched to prevent the deviation from recurring.
Premises and equipment
Under GMP, the facilities chosen for cannabis operations must be deemed appropriate for the manufacturing activities. This has implications ranging from the size of the premises to the hygienic attributes and air-handling capability of the buildings, or greenhouses in the case of cannabis cultivation. Adequate electrical service must be available to power the needs of equipment and HVAC systems. Security of the facility must meet state requirements, including restricted entry to product storage areas and information technology infrastructure, with security camera coverage throughout the premises. Inert surfaces are a central tenant in food handling, hence the popularity of stainless steel in these commercial kitchen-style facilities. Equipment must also be appropriate for the stated purposes required by the manufacturing processes. Logs are associated with each unit requiring routine cleaning. Temperatures of refrigerated and ambient storage areas, and often times humidity, are continuously controlled and documented, ideally with modern digital automated systems readily available these days for exactly this type of environmental conditions monitoring.
Raw materials and in-house quality assurance/quality control (QA/QC)
A central tenet of GMP is the qualification of raw materials before use. Quarantine, an all-too-familiar word these days, here describes the process of segregating and placing holds on externally provided raw materials until their status is known. Suppliers should be vetted in advance by a formalized process during which a determination is made to approve or disapprove engagement. Raw materials range from soil and nutrient amendments at the grow, to baked-good ingredients for edibles, including THC or CBD isolate, oil, or tincture used to infuse products. Soil, as well as nutrient applications, for example, would need to be pre-qualified with a screening test showing non-detects for state-regulated pesticide analytes and Aspergillus mold, Salmonella, and E. coli before use in plant cultivation. Concentrated forms of THC and CBD for infusion into edibles, topicals, and other products would be screened for potency and contaminants before use, in order to ensure the proper formulation and contaminant-free status of the end product. In order to avoid batches that don’t conform to the final concentration specifications of the product, the starting material potency must be verified in-house, in order to confirm the external provider’s stated potency. All these proactive measures pay return-on-investment in the form of fewer failed (or worse, recalled) batches and stability in product quality, which ultimately translates to customer loyalty and sustainability of the brand.
When will GMP be formally required for cannabis production?
In some cannabis-legal states the regulations already point toward existing GMP frameworks that are suitable for cannabis manufacturing businesses. One of the best examples to date is seen in the state of Michigan, which requires compliance with one or more systems associated with food handling for infused or edible product manufacture, including the FDA Food Safety Modernization Act (FSMA) or the International Organization for Standardization (ISO) 22000 standard. Michigan further directs cannabis manufacturers to comply with 21 CFR part 117 and 110 and maintain formulation records for all products, including test results for ingredients used.
In the absence of direct state guidance, voluntary compliance is not uncommon, as brands prepare for the inevitability of oversight at the federal level. While it certainly requires investment in appropriate facilities, equipment, personnel, and documentation systems, the payoff will be a company that withstands the ever-increasing requirements for compliance, accountability, and transparency in cannabis cultivation and manufacturing. The establishment of a culture of commitment to consistent quality for cannabis products now will pay dividends on today’s investment in the industry for years to come.