The Food and Drug Administration is a government agency that uses scientific principals and tools to determine if food items are safe from harmful substances, including human pathogens.  The FDA funds and publishes up to date, relevant, and cutting-edge research investigating microbiology, genomics, toxicology, and chemistry.  This research is geared towards equating the myriad of varying processes and environments that food items and dietary supplements are produced within.  From a biological standpoint, three main bacterial pathogenic genus/species of concern are Escherichia coli, Salmonella spp., and Listeria spp.  Two out of these three types of bacteria have been regularly included within regulated cannabis biological adulteration testing across multiple states and countries.  The third, Listeria spp. which is arguably one of the most resilient to abiotic stress, has not been addressed as widely as the first two types of bacteria.

Bacterial Pathogen – Escherichia coli

The most infamous serotype of pathogenic E. coli is O157:H7, but there are other types that can make consumers sick.  These nasty bugs are transmitted via a fecal to oral route, meaning that they are present in the intestines of animals, including humans.  Contact with excreted material that harbors these germs or contaminated water sources, will result in transmission of E. coli cells, which may colonize cannabis.  This germ is widely associated with beef, however, raw produce that has not been processed via a heat-kill step has been identified as a vehicle for E. coli transmission.  E. coli can be controlled for with a stringent hand washing policy, QC of any organic fertilizers, treated water, and zero animal contact with plants, including instruments that have been in contact with animals.  Vegetative cells can be eradicated with an appropriately monitored dry step, but this will not remove any DNA evidence left behind which can insinuate unsanitary processing conditions. For more information on how drying to an appropriate level of water activity fits into a HACCP program, see this post.

Bacterial Pathogen – Salmonella spp.

According to the FDA’s “Big Bad Bug” book, while Salmonella has traditionally been associated with animal products, there has been a spike in Salmonella outbreaks from produce and ready-to-eat food items.  This is partially owed to the ability of this germ to persist in a dry environment with high plant metabolite content, such as spices.  Salmonella is also transmitted via fecal oral route and there are serotypes that can be found in contaminated water supplies.  Controlling Salmonella is similar to controlling E. coli within a production environment.  Proper hand-washing, QC of raw materials used within the production of cannabis flower, treating the water, and no contact with animals or instruments that have come in contact with animals, is sufficient to control for bacterial pathogen contamination, including Salmonella contamination in most cases.

Bacterial Pathogen – Listeria spp. 

What makes Listeria unique is that serotypes of this genus have the ability to survive in salty environments and grow at temperatures as low as 1° C.  While a majority of recorded outbreaks of this group of bacteria are linked to processed animal products, raw produce can harbor this bacterium as well, along with finished processed food items, such as ice cream.  Like Salmonella, Listeria is a hardy germ, it has been recorded that the same isolates have been isolated from the same production facility over a 12-year span in one case.  There have been instances where the FDA has put a facility on notice or completely suspended facilities that could not control Listeria spp. emergence on the production site, asserting that the environment presented a high level of risk to consumers of products processed within the facility.  Processors must be very diligent in monitoring for this type of bacteria and ensuring that it does not contaminate high traffic areas within a facility or is not already present within a facility to be purchased, as it is particularly difficult to eradicate.  Environmental swab assays can be of major help in finding unwanted microbial species within a cultivation environment so that the area may be thoroughly sanitized and re-swabbed to ensure complete eradication.

Minimizing Risks of Exposure to Bacterial Pathogens

One of the best ways to minimize risks of pathogenic contamination within a supply chain, is to establish an employee hygiene policy that outlines proper hand washing technique, glove use, and reminds employees to stay home when feeling under the weather.  Another way to minimize risk of contamination, is to design the facility to inhibit instances of cross contamination especially where there are raw plant or animal items present within or near the facility.  Facility buildout can be a major boon not only to flow and efficiency of production processing, but also mitigation of biological and chemical cross-contamination.  It is always advisable plan a facility around a process prior to physically building it out, in order to ensure optimal production flow.

Finally, keep in mind that animals such as cows and horses that produce waste that is processed into fertilizer may be infected with E. coli or other pathogens.  Quality checking these items prior to widespread application onto agricultural goods that will be consumed by humans is a fantastic way to ensure that the supply chain is guarded against biological threats.

Contact Us.

Orion GMP Solutions is a Pharmaceutical Engineering Firm based out of Denver Colorado.  We specialize in the implementation and auditing cGMPs for GMP Cannabis Manufacturers.  If you would like to get more information, please send us an email at info@oriongmp.com.

This content was written and sponsored by Orion GMP Solutions.

Hazard Analysis and Critical Control Points.

Hazard Analysis and Critical Control Point (HACCP) program have scientifically established critical limits.  The Codex Alimentarius as well as the National Advisor Committee on Microbiological Criteria of Food both recognize that this systematic approach to food safety consists of three aspects: identification, evaluation, and control.  The aim of an effective HACCP program is to identify points within a process that are essential to producing a safe, high quality product.

Closely monitoring CCPs will ensure that tough decisions about recalls never happen or happens on minimal occasion.  Recalls may occur due to product adulteration or a product being improperly formulated and therefore, still adulterated.  Recall associated risks are mitigated purposefully and methodically when a process has designated points where data is collected and recorded which indicates that action needs to be taken to avoid adulterating a product.  An effective HACCP program is especially critical for high throughput or continuous production lines, batch production lines with high risk for improper compounding or formulation, and batch processes producing end products that are easy to contaminate.  It is interesting to note that the international standard for Food Safety Management System, known as ISO 22000, combines HACCP and ISO 9001:2000 along with pre-requisite programs that GMPs, QMS, and other related programs into a thorough and comprehensive management system.  This addresses facilities from farm to fork.

In 2011, President Obama signed into effect the Food Safety and Modernization Act.  This new legislation shifted the focus of food safety from a responsive one to a preventative and risk-based approach.  FSMA mandated the development of HACCP programs for food producers, beverage producers, farms, and holding points for agricultural goods.  The primary aim is to prevent food-borne illness.  A second aim is to protect the food supply from both intentional and unintentional bioterrorism.

Why do I need a Cannabis HACCP program?

Identifying CCPs, establishing critical limits for CCPs, monitoring CCPs, and record keeping is valuable because it provides additional details about each batch that is produced.  Holding critical control points within a designated range contributes to consistency of product quality.  Scaling up an operation and maintaining product quality and compliance is difficult if processes are not standard and validated with state or federal guidelines intentionally addressed within SOPs and GMPs.  Compiling the recorded data from monitoring CCPs and other critical steps within an SOP into a batch record will prove that quality between batches remains the same.

Developing a strong, thorough, and customized Cannabis HACCP program provides control over a production line, this control is fed by insight into the process on a mostly continuous basis.  Cannabis HACCP programs also establish corrective actions to follow prior to instances where CCPs fall out of their established critical limits.  Having corrective actions already established makes production much smoother, minor issues that can potentially become halts in production flow or decrease end product quality, cease to be large headaches costing hours upon hours of meeting time and back and forth conversations concerning what to do.  Instead, correcting a CCP becomes yet another procedure that is already established and the staff can be trained to handle in a semi-autonomous manner.

Water Activity in Cannabis.

Water activity is the ratio of water vapor pressure in matrix over the vapor pressure of pure water at the same temperature.

It is a measure of the “free water” within a matrix.  Cannabis flowers should be dried to a water activity level less than Aw=.65, if it is not, spoilage microbes can grow on flowers during the cure and give them an undesirable look and smell.  It can possibly even make patients sick and probably will not pass visual inspection by a regulated cannabis lab.

Water Activity’s Critical Limit is AW=.65.

“When we get our flower from harvest, we have to think about the drying and curing process, where mold and bacteria can spoil our harvest,” said Dr. Markus Roggen, Co-Chair of the Scientific Advisory Committee of NCIA and Vice President of Extraction at OutCo.  It has been scientifically proven that decreasing water activity inhibits spoilage microbe growth.  Therefore, water activity should have a value based critical limit that is monitored and logged at multiple points between the initial harvest, the dry process, curing/aging and packaging for distribution.  The critical limit for drying Cannabis flowers is Aw of .65.  An internal standard may be less than this value.  This limit, again, was established to stop growth of bacteria and mold on Cannabis, especially flowers that are intended for combustion.  Control of any critical control point must be considered when engineering a manufacturing process, especially a critical control point that can easily fluctuate and that is entirely dependent upon environmental factors.  Read about the Cannabis HACCP implementation for monitoring water activity that Dr. Roggen completed here.

Mycotoxin Production within Cannabis Batches with Aw>.65.

Too much free water within the cannabis matrix can also allow for metabolizing of secondary metabolites from mold and fungi that may germinate in an environment above Aw=.65.  These metabolites include types of mycotoxin that are not allowed to be present within cannabis matrix intended for any retail or sometimes even further refinement.  Extraction optimization experimentation may reveal an optimal moisture content range, nevertheless, flower water activity should still fall below Aw=.65 if it is going to be stored.  Mycotoxins have been detected within cannabis extract, therefore, flowers with confirmed presence of Aspergillus mycotoxin producing species and testing positive for mycotoxin may not be allowed to be processed into extract and depending on the amount cannot go to market.  Monitoring water activity can help prevent this from occurring.

There are many variables that contribute to variance of product quality within batches of that product.  Identifying critical control points will ensure, at minimum, anything that can be hazardous to human health is monitored and there is assurance that no adulterating or contaminating substances are present.  Limits are established based on solid scientific research often funded by regulating bodies and completed by universities and public health agencies.  The limits should be monitored, and a system established for supervising large scale production environments.

Contact Us.

Orion GMP Solutions is a Pharmaceutical Engineering Firm based out of Denver Colorado.  We specialize in the implementation and auditing cGMPs for GMP Cannabis Manufacturers.  If you would like to get more information, please send us an email at info@oriongmp.com.

This content was written and sponsored by Orion GMP Solutions.

It is easy to become overwhelmed with the idea of working with cannabis in a production environment. Cannabis cultivation itself is complex enough of a process to achieve a high potency flower while still having to go through the drying and curing steps just to ensure you have an optimum final product. All of these steps have inherit risks such as pathogen contamination or mold growth. Establishing procedures with emphasis on cannabis safety principals is not an easy task.  Fortunately, upon temporarily disregarding unique characteristics of cannabis, what remains is what makes cannabis similar to other agricultural goods and commodities.  This is where established solutions and guidelines for production, manufacturing, and regulating of various products can be of use.  

This article presents a broad overview of shelf stability, challenges in producing unadulterated shelf stable cannabis, and techniques utilized in modern food microbiology that will also be utilized within the cannabis industrial space for internal monitoring of critical control points and regulatory screening for biological adulteration.  

Introduction.

For safe consumption purposes, cannabis extracts that are used as stand-alone products and infused into edible products can be considered a food additive or dietary supplement. Placing cannabis into the same space as dietary supplements or nutraceuticals has many advantages because regulations for safe dietary supplements, functional food additives, and “OTCs” are already established by the FDA.  When taking into consideration that tobacco, a combustible product, is regulated by the Center for Tobacco Products housed within the FDA, it becomes apparent that FDA Good Manufacturing Practices and regulations can serve as a wonderful template when looking to establish rigorous standards for cannabis safety and protection against adulterating compounds and materials. 

Food Safety in Modern Times. 

The advent of molecular biology did more than just provide a foundation for the booming biotechnology industry.  It revolutionized the discovery of adulterating microbial species traditionally identified by lengthy plating and counting methods and protocols.  Food microbiology is the scientific study of microorganisms, both in food and used to produce food.  This includes microorganisms that contaminate food.  Food safety is a major focus of food microbiology and these principles are used to produce unadulterated shelf stable food items and agricultural commodities. Cannabis safety is a subset of food safety.

Shelf Stability – HACCP.  

The formal definition of shelf stability pertains to preserved food which is able to be stored at room temperature for long periods of time.  From a manufacturing viewpoint, shelf stability can be seen as a measure of control over the production environment of a product.  It can also be seen as a result of adherence to that food’s established production requirements by a regulating body, such as, in the case of juice where a 5-log reduction of pertinent pathogenic bacteria is mandated by the FDA.  Regulatory guidance for producing shelf stable food items for the public are available on agency websites.

Hazard Analysis and Critical Control Point (HACCP), is a program that evaluates risks of product adulteration.  HACCP addresses biological adulteration (and much more), the FDA currently defines what is “adulterated,” and then the FDA establishes guidelines detailing how to produce a shelf stable product that is not adulterated.  We even see states, such as California, utilizing the terminology “Critical Control Points,” in the newly issued emergency regulations (DPH-17-010E section 40258 – Preventative Controls, page 57 of 97).

In summary, regulatory guidelines are widespread and applicable in all food manufacturing and dietary supplement processes, while HACCP programs are customized to each individual facility or manufacturing plant.  Cannabis producers that are serious about producing high quality GMP cannabis should have a HACCP plan tailored to their production facility with keen focus on cannabis safety. Focusing on cannabis safety when producing shelf stable products will result in consistent, high quality GMP Cannabis products.

Challenges of Producing Shelf Stable Cannabis Products. 

One challenge presented in producing shelf stable GMP cannabis, is that we have established methods for determining spoilage in cannabis, but, methods for producing compliant product are still not widely spread or commonly known.  When considering the multitude of methods used to screen cannabis, microbial standards seem artificially stringent and difficult to achieve.  Some of these methods of identifying microbial species target species that may or may not be present in high concentration, alive, or excreting a toxin that spoils the product.  To make the matter of producing compliant cannabis even more tricky, most methods for decreasing the microbial load on harvested agricultural goods tend to alter the appearance in some form.  While this is acceptable when intending to further process the raw material, cannabis flower producers, specifically boutique flower producers, are under pressure to maintain the beauty of the flower while protecting the flower from adulterants.

Testing Methods for Process Improvement.

There are a myriad of methods for isolating, enumerating, or detecting spoilage microorganisms, but the rationale for considering a batch of a product to be adulterated is still under review and fluctuating.  This leaves the burden of additional due diligence on cannabis producers that most agricultural commodity producers do not face.  Cannabis producers must establish internal standards of quality for their product that meet or hopefully exceed the standards set by regulating bodies while industrial methods for production are still being established and are not widely distributed or accessible.  This is challenging, because food microbiology and food science is not a commonly studied discipline for growers of agricultural commodities. New, rapid, and “consumer friendly” DNA-based technology is a boon to those interested in food safety from biological adulterating microbial species and establishing internal monitoring of critical control points.  It can, however, be tough to interpret these results and determine instances of spoilage, especially when considering the cannabis industry is still laying its regulatory foundation.  

Variance in cannabis testing lab methodology and results can present even more questions when seeking to improve processes.  Interpretation of microbial testing results must first begin with determination of the method utilized to produce the result.  DNA, RNA, protein, and colony enumeration methods all have differing implications, pros, and cons.  The same can be stated for different analytical chemistry instruments and methods.  These attributes must be considered when seeking to improve internal processes.  Regulated cannabis testing laboratory methods of medical and recreational cannabis screening are being standardized and variance between results and labs is being improved, therefore, being cognizant of testing methodology is especially prudent. 

Conclusion.

Cannabis producers may feel that they are being given an impossible task, that becoming compliant with microbial testing standards is challenging and unfair.  Microbial standards are necessary, but cannabis producers, manufacturers, and regulators should expect this task to be easier said than done.  Overcoming microbial spoilage requires understanding of food microbiology, food processing, the ability to identify critical control points, and establishing methods for monitoring these points.  Increasing the safety and quality of products requires adherence to validated processes and GMPs. 

Contact Us. 

Orion GMP Solutions is a Pharmaceutical Process Engineering firm based out of Denver Colorado. We specialize in the implementation and auditing of GMP Cannabis Manufacturers to assist them in reaching international markets. If you would like to get more information, please send us an email at info@oriongmp.com. 

This content was written and supported by Orion GMP Solutions. 

Keeping track of all the biology, chemistry, and engineering used to determine how to produce safe foods, food additives, and botanically derived nutraceuticals can be a complete drain.

Here are 8 GMP Cannabis Safety Tips, that will keep a production environment cleaner, more efficient, and decrease risks of contamination:

Wash your Hands.

Washing your hands before and after handling cannabis, as well as between handling different batches of cannabis, is one of the best steps towards stopping cross contamination of finished product.  Establishing a formal hand washing policy is a great practice that shows commitment to hand hygiene in a production facility as well as protects employee health.

Monitor your Temperatures.

Cook cannabis infused cooking oils or baked goods to proper temperatures that kill bacteria, including Salmonella, Listeria, and the types of E. coli, that cause illness.  Record the temperature for each batch that is generated, then if there is a problem, there are batch records to research or investigate what went wrong and fix it.

Not only is monitoring temperature important for cannabis food products, it is essential for controlling extraction product quality.  Continuous monitoring of temperature during extraction and distillation processing will reduce the risk of the product forming undesirable impurities and cannabinoid breakdown products.

Separate Processed and Unprocessed Material.

Keep any pathogens that could be on unprocessed cannabis from spreading by establishing procedures that keep unprocessed and processed product separate.  Storage in completely different rooms is best for preventing cross contamination.

Be Proactive Against Contamination.

All employees should understand the concept of cross-contamination, it is everyone’s duty to prevent cross contamination within the working environment, and between the work floor and administrative/personnel areas.

Establish Equipment Sanitization Procedures. 

Keep product batches in different containers, and don’t use the same equipment to process them, unless the equipment is appropriately sanitized with an experimentally validated internal sanitization protocol in between processing of different batches.

Establish Work Surface Sanitization Procedures.

Countertops should be appropriately sanitized regularly in accordance with a validated procedure as well.

Say Yes to Environmental Pathogen Swab Tests.

Take proactive actions to monitor the environmental conditions of your production facility.  If a pathogen persists in the production environment, there is a much higher risk of the production area or line being contaminated with that microbial species.  In this instance, ignorance is not bliss.  There are many instances of the same strain found in an outbreak being isolated from high traffic areas within production environments.

Don’t Get Lazy With the Storage.

Store finished product in a cool and dry environment, with a stable and continuously monitored humidity level as soon as possible, post processing.  Remember, the less pathogenic cells present, the less chance they will make a consumer ill.  Proper storage conditions keep most types of bacteria from growing to numbers that can cause illness.

Product Uniformity is the Goal.

Implementing these 8 tips within your production setting will take time, but it is worth it.  Being proactive and diligent of recording important steps within the process places producers in a position of power within the entire process.  Instead of having things go wrong and having to spend precious time testing every single step of a production line, a manager can simply take a look at the batch records to gain clues that will help solve problems much faster.  This data can also assist in improving a process and finally, ensures that each batch is produced under the same conditions, resulting in product uniformity.

Contact Us.

Orion GMP Solutions is a Pharmaceutical Engineering Firm based out of Detroit Michigan.  We specialize in the implementation and auditing cGMPs for GMP Cannabis Manufacturers.  If you would like to get more information, please send us an email at info@oriongmp.com.

This content was written and sponsored by Orion GMP Solutions.