In 1996 California introduced cannabis for medicinal use, opening the doorway to legalization in the United States. Many other countries and cultures have recognized cannabis for its therapeutic properties. and Now, more than a decade into the twenty-first century, has the US began to accept this notion as well.

 

Cannabis is now the fastest growing industry in the United States with sales slated for $7 billion, more than a 25% increase from 2016. A poll by Gallup shows that cannabis approval is up to 60% of the American public in 2016 which is 50% higher than 2011. In 2012 Colorado and Washington State became the first states to have recreationally legal cannabis for consumption by those 21 years of age or older.

 

By 2017 states across the union have recognized cannabis for medicinal use. Currently, 29 states have some form of medicinal cannabis laws in effect with 8 states and the District of Columbia being out right legalized for recreational use.

 

The federal government still has cannabis listed as an illegal schedule I substance with no oversight by the FDA for regulation. With a serious need emerging for regulation, stakeholders in the budding cannabis industry turned to ASTM International in 2015 for a committee to be formed to create standards. ASTM being an internationally recognized body of professionals that lead the way in creation of standards for industries throughout the world for basically every facet of manufacturing, finally accepted the task in 2017 and created D37 the committee on cannabis. For stakeholders in the industry this was a huge step forward in the recognition of cannabis and its legitimacy as a therapeutic drug with widespread medicinal use.

D37 is the officially recognized committee on cannabis with the inaugural meeting on June 11-12, 2017 in Toronto, Canada. The committee is composed six subcommittees to cover all aspects of manufacture of cannabis which was agreed upon during the meeting to vote and create the committee at ASTM headquarters.

 

The six subcommittees cover indoor and outdoor horticulture and agriculture, quality management systems, laboratory, processing and handling, security and transportation, and personnel training, assessment, and credentialing. Each subcommittee is chaired by a leader in each respective field.

 

Those involved in the inaugural meeting all agreed that this is a pivotal point in the industry and the upmost care shall be taken in the development of these standards. Careful consideration will be placed on each and every standard and all stakeholders see this committee as the prime example of what cannabis will be in the next decade.

 

ASTM has chosen to lead the way in bringing cannabis from the taboo underground into the forefront of horticulture manufacturing. D37 will bring standardization into a medicine that so many already desperately depend on and a medicine that so many more need. ASTM has recognized the flaws in an industry that most have a difficult time acknowledging as a legitimate medicine but understands the more information that is available the more likely it is to be accepted. Cannabis is no longer in basements and closets but controlled in multi-million dollar state of the art greenhouses. This will be the medicine of the 21st century and eliminate the dependence on opioids that are destroying so many lives. Stakeholders of the industry see this as the way in to the future and the help so many need.

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Are you interested in participating in ASTM International D37 Cannabis Standards Committee? Send us an email and we will send you a personal invitation to the committee.

Sometimes it’s best to take a step back, and explain basic concepts of the bigger picture – to take a look at the forest instead of just the trees. Good Manufacturing Practices (GMPs) are complicated systems that assure customer safety. Despite being complicated, you can break them down to a simplified concept of what they are, why they exist, and what it looks like for an operator or technician executing a Standard Operating Procedure (SOP).

What is GMP?

GMP stands for Good Manufacturing Practices. It is also commonly referred to as cGMP, meaning that it is the “current Good Manufacturing Practice” that meets GMP requirements as they are currently regulated. They are the set of regulations that describe all of the operations required to call a drug product, a GMP certified product. Any drug you buy at the pharmacy is produced under GMP conditions.

Why are there GMP regulations?

GMP’s are a way to ensure the public’s safety for manufactured drugs, in order to prevent public health crises. It helps prevent the distribution of adulterated drugs, due to poor manufacturing practices, from reaching consumers that whose health could potentially be harmed.

For example, there was a time before GMPs, where a manufacture could substitute whatever they wanted into their “miracle elixers” that were good for soothing all aches and pains. There was no basis for their efficacy, and the ingredients were completely unregulated. This all changed around 1906 when Upton Sinclair wrote “The Jungle,” where he described the filthy and unsanitary conditions of meat packing plants in Chicago. This completely changed how people thought about how things are manufactured.

What does it mean to operate under Good Manufacturing Practices?

Things have changed since the early 1900’s, and we now have processes in place to make sure that no drug or food substance goes out the door of a factory without having close control over the process. There are many concepts packed into an SOP, and many systems that all work together to make the process work.

So, “from the ground up,” here’s what is looks like when a technician or operator works through a GMP process using their SOP’s. Imagine a technician producing and extract using a Supercritical CO2 process or a Cannabis chef producing an edible with a purified extract.

  1. Obtain the proper and current Standard Operating Procedure (SOP) before starting the job. The SOP will guide the technician through the procedure step-by-step, greatly reducing the chance of operator error.
  2. Thoroughly read through the SOP before starting to make sure that nothing has changed for the procedure, and that the right procedure is being used for the right starting materials.
  3. Follow the instructions exactly, and do not change them or deviate from them.
  4. Work accurately and precisely, paying close attention to the details of each step.
  5. Prevent any contamination or mix-up of materials. Do not have two separate batches of raw materials of in-process materials in the same are without being labeled.
  6. Make sure that no products are mislabeled.
  7. Use equipment that’s been cleaned, calibrated, and is the right tool for the job. All equipment should be well maintained and ready to use. If something is not working, it should be labeled “out of service” until it’s ready for use.
  8. Document your work as it is being done, with initials and dates on the SOP for each step.
  9. Keep your workspace clutter free and clean.
  10. Any documented work may not be destroyed – it can be corrected, but never discard it.
  11. If anything does not go according to the SOP, it must be reported to direct supervisors and the deviation must be documented and analyzed for any risks posed to the end user.

These are the most general guidelines for what GMP looks like in practice. While GMPs are a new concept to the recreational and medical cannabis industry, they’re not new to the pharmaceutical industry. It will take time for the industry to catch up, but it’s not hard to do once a company commits to a culture of quality management systems and cGMPs.

If you have more questions, check out www.oriongmp.com and get a free consultation on putting together your Cannabis related Good Manufacturing Practices and Quality Manufacturing Systems.

The Code of Federal Regulations Title 21, Part 210 is dry reading, but it’s necessary for the cannabis industry to digest. Understanding these regulations, despite their dry nature, is the job of the Quality Assurance unit. In fact, it’s optimal that everyone involved in cGMPs is very aware and familiar with this documentation.

For the sake of this writing, my aim is to inform quality assurance (QA) and quality control (QC) personnel of what they need to know. This is a good place to start. You must understand the following definitions in order to read further into the literature of Good Manufacturing Practices.

Code of Federal Regulations Title 21, Part 210 – Current Good Manufacturing Practice in Manufacturing, Processing, Packing, or Holding of Drugs

The 21 CFR 210 and 211 only describe the minimum current good manufacturing practices.

The 21 CFR describes the minimum methods, facilities, and controls that need to be in place for manufacturing, processing, packing, and/or holding any drug product. The main goal is to make sure that drugs are manufactured to the specifications they claim to have – it ensures:

  • Safety
  • Identity and strength
  • Quality and purity characteristics

As usual, there’s a consequence for not following the rules, which can be very costly. If it’s found that a company manufacturing under cGMPs is not complying with the 21 CFR, they may:

  • Determine the drug is adulterated
  • Hold the person responsible who was in charge of the process

When your company is found to be violating the 21 CFR, you might get a publicly published 483 warning letter that will say something along the lines of:

“You should take prompt action to correct the violations cited in this letter. Failure to promptly correct these violations may result in legal action without further notice, including, without limitation, seizure and injunction.”

Right now, cGMPs for the cannabis industry are in their infancy. When the FDA is regulating the industry, it will be a different story.

Definitions

When you fully understand these terms, you will have a much easier time understanding the 21 CFR part 211. It’s the baseline of information that sets the stage for everything that’s to come. Take warning though – these are complicated definitions, and often require a background in chemistry or the sciences to fully understand.

Some definitions will be followed by an explanation tying it into terms related to the cannabis industry, as necessary.

Batch – a specific quantity of a drug or other material that is intended to have uniform character and quality, within specified limits, and is produced according to a single manufacturing order during the same cycle of manufacture.

This could be a batch of plants that finished their flowering period at the same time, and were harvested at the same time. Alternatively, it could be the finished extract that was produced by one cycle of a CO2 or hydrocarbon extraction system.

Component – any ingredient intended for use in the manufacture of a drug product, including those that may not appear in the final drug product.

This could be the CO2 or butane used in an extraction.

Drug Producta finished dosage form, for example, tablet, capsule, solution, etc., that contains an active drug ingredient generally, but not necessarily, in association with inactive ingredients. The term also includes a finished dosage form that does not contain an active ingredient but is intended to be used as a placebo.

This could be flowers that have been fully processed to their dried and cured form, ready for use. It could also be an extract that has been fully purged, packaged, and labeled, ready for use.

Fiber any particulate contaminant with a length at least 3X greater than its width.

Nonfiber releasing filterany filter, which after appropriate pretreatment such as washing or flushing, will not release fibers into the component or drug product that is being filtered.

Active ingredient – any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or other animals. The term includes those components that may undergo chemical change in the manufacture of the drug product and be present in the drug product in a modified form intended to furnish the specified activity or effect.

In the case of cannabis, this would be all the cannabinoids that are present in the final product. Cannabis is tricky in that its final forms are usually a mixture of cannabinoids, and not pure product. All together, the mixture of cannabinoids can be considered the active ingredient.

Inactive ingredient – any component other than an active ingredient.

In the case of cannabis flowers, it would be everything but for the cannabinoids. In the case of an extract, there can be waxes and other lipids that are present with the active ingredient.

In-process material any material fabricated, compounded, blended, or derived by chemical reaction that is produced for, and used in, the preparation of the drug product.

In general, there are purification steps involved in producing cannabis products, and relatively few chemical reactions.

Lota batch, or a specific identified portion of a batch, having uniform character and quality within specified limits; or, in the case of a drug product produced by continuous process, it is a specific identified amount produced in a unit of time or quantity in a manner that assures its having uniform character and quality within specified limits.

Similar to a batch, but is the result of a continuous process. Therefore, a lot would be the packaged components from, for example, 100 bottles filled with cannabis tinctures. The tinctures would be filled in a continuous process and all 100 would be filled in a specific identified amount of time or quantity.

Lot number, control number, or batch number any distinctive combination of letters, numbers, or symbols, or any combination of them, from which the complete history of the manufacture, processing, packing, holding, and distribution of a batch or lot of drug product or other material can be determined.

This is the identifying number of a lot or batch. It’s a locally produced number that’s used to track all activity that was associated with manufacturing a drug substance.

Manufacture, processing, packing, or holding of a drug product includes packaging, labeling operations, testing, and quality control of drug products.

Quality control unit – any person or organizational element designated by the firm to be responsible for the duties relating to quality control.

Strength

  1. The concentration of the drug substance (e.g. weight/weight, weight/volume, or the unit dose/volume basis).
  2. The potency, i.e., the therapeutic activity of the drug product as indicated by appropriate laboratory tests or by adequately developed and controlled clinical data (e.g. expressed in terms of units by reference to a standard).

Theoretical yield the quantity that would be produced at any appropriate phase of manufacture, processing, or packing of a particular drug product, based upon the quantity of components to be used, in the absence of any loss or error in actual production.

Actual yieldthe quantity that is actually produced at any appropriate phase of manufacture, processing, or packing of a particular drug product.

Percentage of theoretical yield – the ratio of the actual yield (at any appropriate phase of manufacture, processing, or packing of a particular drug product) to the theoretical yield (at the same phase), stated as a percentage.

Acceptance criteriathe product specifications and acceptance/rejection criteria, such as acceptable quality level and unacceptable quality level, with an associated sampling plan, that are necessary for making a decision to accept or reject a lot or batch (or any other convenient subgroups of manufactured units).

Representative sample – a sample that consists of a number of units that are drawn based on rational criteria such as random sampling and intended to assure that the sample accurately portrays the material being sampled.

 

If you have more questions, check out www.oriongmp.com and get a free consultation on putting together your Cannabis related Good Manufacturing Practices and Quality Manufacturing Systems.

It’s always a pleasure when I get an email from someone asking how to break into the industry. I can appreciate the feeling – I was once there. I had hustle, and always worked hard, but I didn’t have a clear vision of the end game.

Ultimately, building yourself up in any industry requires experience. You dig into the work and make a name for yourself. There are many ways to get there, but it’s usually a nonlinear process.

I got my start in the industry in an unlikely place – as a Sergeant in the Marine Corps. I realized during my last tour in Iraq that the cannabis industry was in my future. I had my own personal reasons that drove me towards it, but I saw things lining up. I was honorably discharged in 2006, and I immediately got to work on my education in both cannabis and chemistry.

I hadn’t taken a math class in 5 years, and I had no real background in the sciences. Despite that, I started from the bottom and worked my way through all the liberal arts, math, chemistry, and biology courses. I hustled, and my work paid off with the rewards of leading chemistry study groups – I found that teaching is one of the most rewarding things I can do.

I attended the University of Michigan where I studied Biochemistry and spent my free time learning about the physiology of the endocannabinoid system. I wanted to learn everything about how cannabinoids affect the body and their therapeutic potential. I graduated with my B.S. in 2011 and tasted the accomplishment of my hard work. I planned on going through to a PhD program in Biomedical Sciences, but I first wanted to solid foundation in scientific research before jumping into it.

That’s where some luck comes into play. I landed a job in a biochemistry/genetics laboratory at the University of Michigan where I had the best mentors a young scientist could have. I had all the tools of the trade for HPLC, column chromatography, mass-spec, and a project that needed me to use all of them. I was a protein chemist. Every purification started with extractions, and moved on through multiple steps of column chromatography that ended with HPLC purification.

Andrew - Research day - 2014 poster - Final

I scaled up processes and thought of myself as the Henry Ford of protein purification… Perhaps it was grandiose to think that way. Nonetheless, it’s where I learned to apply the scientific method on a daily basis, and I where I got my basic understanding for extracting and purifying compounds.

I found that a career in academic science was not for me. It is a surprisingly political atmosphere, and I’m not one for bickering. I was accepted into a PhD program, but dropped out just days before the program started. I knew it wasn’t right for me, and, besides, I had an awesome job in the pharmaceutical industry as a Good Manufacturing Practices Quality Control Chemist. It was there, that I realized Good Manufacturing Practices (GMPs) are the future of the cannabis industry – I finally had my clear vision of the end game.

I always kept myself busy moonlighting in the industry while working as a chemist by day. I put the two together, and found that my best bet was to share information and help other people. HempHacker has become my means of teaching people about different aspects of the industry that aren’t fully covered elsewhere.

Since my last job as a GMP QC Chemist, I’ve been doing GMP Consulting for the Cannabis industry. It aligns all my criteria for a job that’s good for me. I’m able to travel, meet new people, help them with their projects, and do a lot of networking in the industry. It’s also very satisfying to know that my work has a positive impact on the quality of products. It’s a very rewarding job for me.

I’m happy with the way it happened, but I know that I would have different advice for someone starting out now. In my next post, I’ll give my suggestions for people getting their start in the industry. I hope it’ll help people get an advanced start.

Compliance vs. Good Manufacturing Practices

Just to clarify, there is a difference between Compliance and Good Manufacturing Practices (GMPs). To put it simply, Compliance covers the laws that allow a company to manufacture cannabis and its products, while GMPs provide a framework for how you do it.

Compliance is presently defined as the state by state rules for manufacturing cannabis and cannabis products. It covers the regulations, required transparency, laws, policies, requirements, and standards for manufacturing cannabis. This sets the legal framework for how businesses in their respective states can operate.

Good Manufacturing Practices, on the other hand, are guidelines that come from the Food and Drug Administration and the International Conference on Harmonization. Both provide the requirements for a pharmaceutical manufacturing operation to produce drugs that will be ingested by human beings. They set the operational framework for how to manufacture drugs that are safe for human consumption.

There are also some similarities. Both Compliance and GMPs can have Standard Operating Procedures (SOPs). SOPs are simply the documentation of any process that a company does. They range from simple to complicated. It can be an SOP for sweeping the floors, or an SOP for a 32 step organic chemistry synthesis of tetrahydrocannabinol.

Compliance is without a doubt, the most important first step to establishing your business. Without it, you can face serious legal consequences. Establish your company with a trusted attorney who specializes in compliance, and start manufacturing with peace of mind.

GMPs are the next best step to make your business stand out above the competition – being a GMP Certified facility creates a huge differentiation in your product. With a well defined GMP system in place, you can track improvements to your product over time using the scientific method, ensure consumer safety, and have fully traceable processes. Overall, it’s a win-win adaptation to your business because you improve your processes (and chances to be bought out) and you improve product safety and quality for the consumer (sell more product).

If you have more questions, check out www.oriongmp.com and get a free consultation on putting together your Cannabis related Good Manufacturing Practices and Quality Manufacturing Systems.

GMP Training for Cannabis Manufacturing and Testing

GMP training is an important part of manufacturing and testing pharmaceutical products. It is the means of ensuring employees can properly perform their job to specified standards. Those standards ensure products are manufactured consistently, in a controlled manner, and to defined quality specifications. Training employees on a regular schedule, with job specific instruction, and thorough documentation help companies meet their standards of manufacturing and testing of their pharmaceutical products.

The first component to a quality training program is that training occurs on a recurring basis. When a new employee joins a company, it is necessary for them to learn, understand, and be tested on their job specific duties. After initial training they are qualified to do their job. They will then be required to perform refresher training that makes sure they are still up to date with any changes to the processes used for their job. For example, if a process is changed, the employee needs to have documented training on the change, proving they understand the change and can employ the process properly.

The second component to a quality training program is that the training covers the scope of an employee’s job. Each employee has their own specialized tasks in a manufacturing or testing facility, and they are responsible for knowing their job as it’s defined by the company. For example, a quality control chemist does not need to know the intricacies of a process chemist’s job, and vice versa. Each respective chemist needs to fully understand their own job so they can perform it up to the standards set in training.

Recurring training is a standard element of any quality process in the pharmaceutical industry. The proof of that training is in documentation. Documentation consumes a large amount of time in a quality manufacturing and testing environment. It is not fun and few people like it. It can take more time than the work itself. Still, without documentation, there is no proof of what has been done. It is important that companies have a documented training program that outlines each job in the company. Each job will have specific duties associated with it, and each duty requires training.

This article isn’t meant to touch on the qualifications of individuals bring to a job, but it grazes an interesting point. People who may not be qualified to start in a job can become qualified. An employee may not know how to operate a Gas Chromatography (GC) instrument when they start the job, but if they know how to operate an HPLC, there’s little reason why they can’t be trained to run a GC. On the job training (OJT) is a viable way to build up your employees’ capabilities and careers. When OJT is well documented, it’s the proof of a person’s education. It’s not only important to prove that your process is being executed by properly trained employees, but it’s also important to your employees’ careers.

If you have more questions, check out www.oriongmp.com and get a free consultation on putting together your Cannabis related Good Manufacturing Practices and Quality Manufacturing Systems.