Soapbox

Are LED Grow Lights Worth It?

By Dr. Zacariah Hildenbrand, Robert Manes
13 Comments

There really is no question that Light Emitting Diodes (LEDs) work, but just how well do they work?

For the last 50+ years, indoor cannabis cultivators have used High Pressure Sodium (HPS) lights to illuminate their flowering crops. This technology was developed for, and is still used, as street lighting and there really hasn’t been a fundamental change to the output in the last half century.LED technology showed great promise to solve some of the primary drawbacks to the use of HPS technology for indoor cannabis cultivation. 

We are often asked why this technology was used to grow cannabis, and the answers are simple: 1) due to strict legislation and even stricter penalties for growing cannabis, growers wished to move their crops indoors, and, 2) there really hasn’t been another technology that would allow us to cheaply place 400, 600, or even 1000W of light on a crop. In addition, HPS technology is rich in certain frequencies of red light, which is so important to flowering crops. Unfortunately, HPS lamps have their drawbacks, such as high heat output and lack of other “colors,” along the lighting spectrum. In fact, up to 95% of light produced by an HPS lamp is emitted in the infrared range, which we perceive as heat.

Enter the Light Emitting Diode. LED technology showed great promise to solve some of the primary drawbacks to the use of HPS technology for indoor cannabis cultivation. The ability to manipulate spectrum, precision delivery of light, elimination of dangerous heat, and lack of substantive toxic chemical makeup are a few reasons to deploy LEDs. However, as with any new technology, there were some significant hurdles to overcome.

Early experimentation using Light Emitting Diodes (LEDs) to grow cannabis, suffice to say, did not go well.  Poor performance, misleading advertising and equipment failures plagued the first mass-produced LED grow lights. The aspect of poor performance can be blamed on several factors, but the most prominent are very low efficacy, in terms of light produced per Watt consumed, and incorrect application of spectrum (color) for horticultural purposes. Causes of “misleading advertising” was a mixed bag of dubious sales pitches and lack of understanding the technology and of horticultural lighting requirements. Additionally, there certainly were some quality control issues with LEDs and electronics equipment in general, especially from offshore manufacturers in China and Korea.

A plant in flowering under an LED fixture

That legacy of poor performance still has a partial hold on the current indoor cannabis cultivation industry. Many of the current “Master Growers” have tried LEDs at some point and for the various reasons mentioned above, reverted to HPS lighting. Some of this reluctance to embrace LEDs comes from unfamiliarity with application of the technology to grow better cannabis, while some can be attributed to stubbornness to deviate from a decades-long, tried-and-true application of HPS lighting.

Certainly, growing with LEDs require some changes in methodology. For instance, when using true “full spectrum” grow lights, more nutrients are consumed. This is caused by stimulation of more photoreceptors in plants. To further explain, photoreceptors are the trigger mechanisms in plants that start the process of photosynthesis, and each photoreceptor is color/frequency-dependent. True full spectrum LED systems fulfill spectrum shortages experienced with HPS technology. Anyone that grows with LEDs will at some time experience “cotton top,” or bleaching at the upper regions of their plants.  Increased nutrient delivery solves this issue.

As we continue to uncover the vast medical potential of cannabis, precise phytochemical composition and consistent quality will become all-important.While the industry is still saturated with confusing rhetoric and some poorly performing equipment, LEDs are gaining momentum in the cannabis market. LED efficacies have increased to levels far greater than any other lighting technology. Broad spectrum white and narrow-frequency LEDs in all visible (and some invisible to the human eye) colors are being produced with great precision and consistency. Quality control in manufacturing is at an all-time high and longevity of LEDs has been proven by the passage of time since their introduction as illumination sources.

As the world embraces LED horticultural lighting, probably the most encouraging news is that current and upcoming generations of cannabis growers are more receptive to new ideas and are much more tech-savvy than their predecessors. Better understanding of cannabis-related photobiology is helping LED grow light manufacturers produce lighting that increases crop yields and perhaps more importantly, cannabis quality. As we continue to uncover the vast medical potential of cannabis, precise phytochemical composition and consistent quality will become all-important.

Obviously, the indoor cannabis industry is expanding rapidly and this expansion raises deep environmental concerns. More power is being used for indoor lighting, and for the cooling required by this lighting. Power systems are being taxed beyond forecasts and in some cases, beyond the capabilities of the infrastructure and power companies’ ability to produce and deliver electricity.  Some states have proposed cannabis-related legislature to limit power consumed per square foot, and some are specifically requiring that LEDs be used to grow cannabis. While some business leaders and cultivation operators may groan at the acquisition cost and change in operating procedures when deploying LEDs, common sense states that it is imperative we produce cannabis applying the most environmentally friendly practices available.

Dr. Ed Askew
Soapbox

Distillation Of Your Cannabis Extract: Ignorance Is Not Bliss

By Dr. Edward F. Askew
2 Comments
Dr. Ed Askew

In a previous article I discussed the elephant in the room for clients of laboratory services- the possibility of errors, inaccurate testing and dishonesty.

Now, I will explain how the current “smoke and mirrors” of distillation claims are impacting the cannabis industry in the recreational and medical areas. We have all heard the saying, “ignorance is bliss.” But, the ignorance of how distillation really works is creating misinformation and misleading consumers.

That is, just because a cannabis extract has been distilled, doesn’t mean it is safer.There have been reports of people claiming that “Distilled cannabis productsthat are Category 2 distillate are pesticide free and phosphate free, while Category 1 has pesticides and phosphates, but within acceptable limits”

The problem is that these claims of Category 1 and Category 2 cannot be proven just by saying they are distilled. Ignorance of the physical chemistry rules of distillation will lead to increased concentrations of pesticides and other organic contaminants in the supposedly purified cannabis distillate. That is, just because a cannabis extract has been distilled, doesn’t mean it is safer.

So, let’s look at a basic physical chemistry explanation of the cannabis distillation process.

  • First off, you must have an extract to distill. This extract is produced by butane, carbon dioxide or ethanol extraction of cannabis botanical raw material. This extract is a tarry or waxy solid. It contains cannabinoids, terpenes and other botanical chemicals. It will also contain pesticides, organic chemicals and inorganic chemicals present in the raw material. The extraction process will concentrate all of these chemical compounds in the final extract.
  • Now you are ready to distill the extract. The extract is transferred to the vacuum distillation vessel. Vacuum distillation is typically used so as to prevent the decomposition of the cannabinoid products by thermal reactions or oxidation. Under a vacuum, the cannabinoids turn into a vapor at a lower temperature and oxygen is limited.
  • Part of the vacuum distillation apparatus is the distillation column. The dimensions of this column (length and width) along with the packing or design (theoretical plates) will determine the efficiency of distillation separation of each chemical compound. What this means is that the more theoretical plates in a column, the purer the chemical compound in the distillate. (e.g. Vigreux column = 2-5 theoretical plates, Oldershaw column = 10-15 plates, Sieve plate column = any number you can pay for).
  • The temperature and vacuum controls must be adjustable and accurate for all parts of the distillation apparatus. Failure to control the temperature and vacuum on any part to the apparatus will lead to:
    • Thermal destruction of the distillate
    • Oxidation of the distillate
    • Impure distillate

Now, you can see that a proper distillation apparatus is not something you throw together from a high school chemistry lab. But just having the proper equipment will not produce a pure cannabis product. The physical chemistry that takes place in any distillation is the percentage a chemical compound that occurs in the vapor phase compared to the percentage in liquid phase.So, how can you produce a cannabis distillate that is clean and pure?

For example, let’s look at whiskey distillation. In a simple pot still, alcohol is distilled over with some water to produce a mixture that is 25%-30% ethanol. Transferring this distillate to an additional series of pot stills concentrates this alcohol solution to a higher concentration of 85%-90% ethanol. So, each pot still is like a single theoretical plate in a distillation column.

But, if there are any chemical compounds that are soluble in the vapor produced, they will also be carried over with the vapor during distillation. This means that pesticides or other contaminants that are present in the cannabis extract can be carried over during distillation!

So, how can you produce a cannabis distillate that is clean and pure?

  • Produce a cannabis extract that has lower concentrations of bad chemicals. Since a lot of the cannabis extracts available for distillation are coming from grey-black market cannabis, the chances of contamination are high. So, the first thing to do is to set up an extraction cleanup procedure.
    • An example of this is to wash the raw extract to remove inorganic phosphates. Then recrystallize the washed extract to remove some of the pesticides.
  • Make sure that the distillation apparatus is set up to have proper temperature and vacuum controls. This will limit production of cannabis decomposition products in the final distillate.
  • Make sure your distillation apparatus has more than enough theoretical plates. This will make sure that your cannabis distillate has the purity needed.
  • Finally, make sure that the staff that operates the cannabis distillation processes are well trained and have the experience and knowledge to understand their work.

Inexperienced or under-trained individuals will produce inferior and contaminated product. Additional information of extract cleanup and effective vacuum distillation can be obtained by contacting the author.

Dr. Ed Askew
From The Lab

Quality Plans for Lab Services: Managing Risks as a Grower, Processor or Dispensary, Part 5

By Dr. Edward F. Askew
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Dr. Ed Askew

Protection in the Court of Public Opinion

In the last four articles, I have outlined areas that impact your operations as they apply to laboratory quality programs. But this article will take a different path. It will focus on protecting your crop and brand along with any business that utilizes your crop, such as dispensaries or edible manufactures in the court of public opinion.

Now, the elephant in the room for cannabis companies is the difference between rules written by the state and their enforcement by the state. There are many anecdotal stories out there that can be used as case studies in identifying ways to protect your brand. Remember, consumers and the media caught them, not the regulators.

Cheating in the cannabis industry: growers, dispensaries, edibles manufactures, etc. This includes:

  1. Finding laboratories that will produce results that the client wants (higher potency numbers)
  2. Not testing for a particular contaminant that may be present in the cannabis product.
  3. Selling failed crops on the gray or black market.
  4. Claiming to regulators that the state rules are unclear and cannot be followed (e.g. So, give me another chance, officer)

So why should you be worried? Because, even if the state where you operate fails to enforce its own rules, the final end-user of your product will hold you accountable! If you produce any cannabis product and fail to consider these end-users, you will be found out in the court of public opinion by either the media or by the even more effective word of mouth (e.g. Social Media).

So, let’s take a look at some recent examples of these problems:

  1. “Fungus In Medical Marijuana Eyed As Possible Cause In California Man’s Death”
  2. “Pesticides and Pot: What’s California Smoking?”
  3. “Buyers beware: California cannabis sold Jan. 1 could be tainted”

Each of these reports lists contamination by microbial stains or pesticides as being rampant within the California market whose products are used for medical or recreational use. Just imagine the monetary losses these cannabis businesses faced for their recalled cannabis product when they got caught. Remember, consumers and the media caught them, not the regulators.Institute a quality program in your business immediately.

How can you be caught? There are many different ways:

  1. Consumer complaints to the media
  2. Secret shopper campaigns (more to come on that in the next article)
  3. Media investigations
  4. Social media campaigns

What are the effects on your business? Product recalls such as these two to hit the California market recently.

So, what should you do to produce an acceptable product and provide reasonable protection to your cannabis business? Institute a quality program in your business immediately. This quality program will include areas of quality assurance and quality control for at least these areas.

  1. Growing
  2. Processing or formulating
  3. Shipping
  4. Dispensing
  5. Security
  6. Training of staff
  7. Laboratory services

Setting up and supporting these programs requires that your upper management impose both a rigorous training program and make employee compliance mandatory. Otherwise, your business will have an unreasonable risk of failure in the future.

Further information on preparing and instituting these types of quality assurance and quality control programs within your business can be found at the author’s website.

Dr. Ed Askew
From The Lab

Quality Plans for Lab Services: Managing Risks as a Grower, Processor or Dispensary, Part 4

By Dr. Edward F. Askew
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Dr. Ed Askew

In the last three articles, I discussed the laboratory’s responses or defenses used to reply to your questions about laboratory results that place stress on the success of your business. The Quality Control (QC) results can cause this stress if they are not run correctly to answer the following questions:

  1. Are the laboratory results really true?
  2. Can the laboratory accurately analyze sample products like my sample?
  3. Can the laboratory reproduce the sample results for my type of sample?

Now let’s discuss the most important QC test that will protect your crop and business. That QC sample is the Matrix Sample. In the last article in this series, you were introduced to many QC samples. The Matrix Sample and Duplicate were some of them. Take a look back at Part 3 to familiarize yourself with the definitions.

The key factors of these QC sample types are:

  1. Your sample is used to determine if the analysis used by the laboratory can extract the analyte that is being reported back to you. This is performed by the following steps:
    1. Your sample is analyzed by the laboratory as received.
    2. Then a sub-sample of your sample is spiked with a known concentration of the analyte you are looking for (e.g. pesticides, bacteria, organic chemicals, etc.).
    3. The difference between the sample with and without a spike indicates whether the laboratory can even find the analyte of concern and whether the percent recovery is acceptable.
    4. Examples of failures are from my experiences:
      1. Laboratory 1 spiked a known amount of a pesticide into a wastewater matrix. (e.g. Silver into final treatment process water). The laboratory failed to recover any of the spiked silver. Therefore the laboratory results for these types of sample were not reporting any silver, but silver may be present. This is where laboratory results would be false negatives and the laboratory method may not work on the matrix (your sample) correctly. .
      2. Laboratory 2 ran an analysis for a toxic compound (e.g. Cyanide in final waste treatment discharge). A known amount of cyanide was spiked into a matrix sample and 4 times the actual concentration of that cyanide spike was recovered. This is where laboratory results would be called false positives and the laboratory method may not work on the matrix (your sample) correctly.
  2. Can the laboratory reproduce the results they reported to you?
    1. The laboratory needs to repeat the matrix spike analysis to provide duplicate results. Then a comparison of the results from the first matrix spike with its duplicate results will show if the laboratory can duplicate their test on your sample.
      1. If the original matrix spike result and the duplicate show good agreement (e.g. 20% relative percent difference or lower). Then you can be relatively sure that the result you obtained from the laboratory is true.
      2. But, if the original matrix spike result and the duplicate do not show good agreement (e.g. greater than 20% relative percent difference). Then you can be sure that the result you obtained from the laboratory is not true and you should question the laboratory’s competence.

Now, the question is why a laboratory would not perform these matrix spike and duplicate QC samples? Well, the following may apply:

  1. These matrix samples take too much time.
  2. These matrix samples add a cost that the laboratory cannot recover.
  3. These matrix samples are too difficult for the laboratory staff to perform.
  4. Most importantly: Matrix samples show the laboratory cannot perform the analyses correctly on the matrix.

So, what types of cannabis matrices are out there? Some examples include bud, leaf, oils, extracts and edibles. Those are some of the matrices and each one has their own testing requirements. So, what should you require from your laboratory?

  1. The laboratory must use your sample for both a matrix spike and a duplicate QC sample.
  2. The percent recovery of both the matrix spike and the duplicate will be between 80% and 120%. If either of the QC samples fail, then you should be notified immediately and the samples reanalyzed.
  3. If the relative percent difference between the matrix spike and the duplicate will be 20% or less. If the QC samples fail, then you should be notified immediately and the samples should be reanalyzed.

The impact of questionable laboratory results on your business with failing or absent matrix spike and the duplicate QC samples can be prevented. It is paramount that you hold the laboratory responsible to produce results that are representative of your sample matrix and that are true.

The next article will focus on how your business will develop a quality plan for your laboratory service provider with a specific focus on the California Code Of Regulations, Title 16, Division 42. Bureau Of Cannabis Control requirements.

Soapbox

5 Things You Can Do To Get the Most Value From Your Consultant

By Vince Sebald
1 Comment

I worked for about 18 years as a company employee in various levels from entry-level engineer to senior director. Since then I have spent over a decade as a consultant in the life science industry as the founder of Sebald Consulting. Presently, I also use consultants as CEO of GxPready!, a web based CMMS software company. Based on this experience, I have put together a top 5 list of things you can do to get the most value when using consultants:

1. Recognize when a project requires a consultant

There can be several reasons a project may benefit from having a consultant which may include bringing a new skill set, industry experience or an outside perspective to bear on a project that is not available otherwise.

Provide clear guidance as to what the task and deliverables are on an ongoing basis.Also, there are occasions when resources are already stretched and you need short-term support to get through an intensive segment of a project, but the work may not be enough to justify additional longer-term resources.

In any of these cases, filling the gap internally can be difficult and time consuming. A consultant can be a great solution. Even if you don’t plan to use a consultant for the project, it may be to your benefit to have a consultant perform a “gap assessment” to help you to identify areas which require improvement to meet compliance requirements or best practice guidelines. This is often done to prepare for audits, for example.

2. Vet the consultant to get a good match

Contact potential consultants to determine if they have the set of skills you are looking for and if they fit within the culture of your organization. Talk to the actual consultant you will be working with before bringing them on.  Review the consulting contract carefully to make sure the terms are mutually acceptable.  Often consultants have some flexibility to accommodate different project situations.

One advantage to using consultants is that you don’t have a long commitment so even after you vet them with interviews, you can work on small projects and gauge the results. Some consulting companies are very formal and others are less so, for example. A good fit is better for both parties. It’s not just the competence, but the culture and personal fit with your team.

3. Provide the consultant with appropriate guidance and resources

Help the consultant give you the best results possible by providing access to the resources (personnel, information, documents, systems, etc.) to allow the consultant to perform the tasks.

Consultants can help you get through unfamiliar territory or help you to manage your team’s workload. Know how to use these resources to benefit your projects. This project manager called just in time.

Provide clear guidance as to what the task and deliverables are on an ongoing basis.

Alternatively, allow the consultant to manage the project and reach out as necessary. Any guidance and resources you can provide the consultant will increase the effectiveness and help control your costs on the project.

If you don’t know exactly what needs to be done (“That’s why I hired a consultant!”) then have the consultant put together a list for you based on some general guidance and then work from that list to get your job completed.

4. Track progress with appropriate level of detail

If you have vetted and hired a consultant, chances are they are going to put in their best effort to meet your requirements. Nonetheless, it is good practice to have a system in place to track hours/costs.

Whether it is weekly reporting, or based on milestones and project updates, this helps to avoid any misunderstandings and provides opportunities for communication of project issues in addition to whatever project updates may be scheduled.

You want your team of consultants and employees to be able to work as well as possible together.Recognize that you can go overboard in this area, working against yourself and the project, if the tracking is so detailed that it takes excessive resources to document. It is definitely possible to inadvertently generate more hours (and expense) by managing time in too much detail. If the concern is high and heavy management is required, perhaps that indicates the consultant is not the best match for this project.

Generally, you can find a good balance with a simple up-front chat with the consultant to review your expectations, and for larger projects it is often formalized in the contract.

5. Recognize if it’s not a good fit

There are many consultants and clients out there. Inevitably, there are times when, despite best intentions, the consultant/client mix isn’t working out. Make sure the contract allows for management of this situation. Can you cancel the contract with reasonable notice? Is there a mechanism for being able to replace members of the team that aren’t working out?

You want your team of consultants and employees to be able to work as well as possible together. If that’s not happening, recognize it and make adjustments as necessary. But don’t lose the contact information. A consultant that doesn’t work out today may be just right for your next project!

Following the above can improve your chances of success with consultants you may hire and allow you to build a solid set of resources you can call on from time to time as things change in your company. Consultants can fill a vital role for tasks requiring specialized skills or short-term projects where a full time hire is not practical.

Maureen Smyth headshot
Soapbox

Raising the Standard for Dispensary Education: Building a Better Budtender

By Maureen Smyth
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Maureen Smyth headshot

At the National Cannabis Industry Association’s (NCIA) Cannabis Business Summit and Expo last week there was a presentation titled, “Raising the Standard for Dispensary Education: Building a Better Breed of Budtender.” Speakers included Adam Cole, learning and development specialist at Native Roots Dispensaries and Dr. Aseem Sappal, provost and dean of faculty at Oaksterdam University. Nancy Whiteman, owner of Wana Brands, was the moderator. Let’s look at some of the ways they have standardized their process in cannabis retail education.Health effects achieved in one patient are not always replicated for every patient. This is true of all medicine.

The standard education module at Native Roots (20 retail locations throughout Colorado, and were awarded licenses in Manitoba, Canada) for onboarding a budtender includes laws and compliance, ID checking and sales limits, customer service and physical effects. Oaksterdam University provides cannabis education and focuses on botany, introduction to the endocannabinoid system, bioavailability, CBD, and edibles vs. smoking as a delivery mechanism. In addition to the already mentioned classes, Wana Brands also teaches the concept of sustained release and capsules (due to product specificity). The Native Roots educational program contains continuing education in the history of cannabis, the endocannabinoid system, methods of consumption, phytocannabinoids and terpenes. For those of you in medical professions beginning your cannabis education, these modules provide a great outline to launch your own learning and development program.

How can dispensaries integrate the medical profession at the point of distribution?The presentation highlighted the legal aspects of providing cannabis information and cannabis products. A licensed medical professional oversees all educational content and everything is run through a legal department. It is important that all cannabis providers use language that offers no definitive medical outcomes. Health effects achieved in one patient are not always replicated for every patient. This is true of all medicine. At Native Roots Dispensary, they address symptoms not diseases. They have specific language to avoid giving medical advice. For good reason, there is a state regulatory body called the Marijuana Enforcement Division (MED) that oversees dispensaries and their adherence to the “no medical advice” decree, along with a slew of other regulatory compliance issues.

Dispensaries offer careful symptom-based product recommendations to many types of consumers. How can dispensaries integrate the medical profession at the point of distribution? Native Roots has partnerships with doctors and the Rocky Mountain Cancer Institute. Additionally, the CEO of Wana Brands mentioned the use of medical kiosks in some dispensaries. My question to Adam Cole was, “Would you like to see trained cannabis nurses on staff or on board as a consultant in dispensaries to deal with patients and have the budtenders service the customer?” His answer: “Absolutely.”

Dr. Ed Askew
From The Lab

Quality Plans for Lab Services: Managing Risks as a Grower, Processor or Dispensary, Part 3

By Dr. Edward F. Askew
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Dr. Ed Askew

Editor’s Note: The views expressed in this article are the author’s opinions based on his experience working in the laboratory industry. This is an opinion piece in a series of articles designed to highlight the potential problems that clients may run into with labs. 

In the last two articles, I discussed the laboratory’s first line of defense (e.g. certification or accreditation) paperwork wall used if a grower, processor or dispensary (user/client) questioned a laboratory result and the conflicts of interest that exist in laboratory culture. Now I will discuss the second line of defense that a laboratory will present to the user in the paperwork wall: Quality Control (QC) results.

Do not be discouraged by the analytical jargon of the next few articles. I suggest that you go immediately to the conclusions to get the meat of this article and then read the rest of it to set you on the path to see the forest for the trees.

QC in a laboratory consists of a series of samples run by the laboratory to determine the accuracy and precision of a specific batch of samples. So, to start off, let’s look at the definitions of accuracy and precision.QC Charts can provide a detailed overview of laboratory performance in a well-run laboratory.

According to the Standard Methods for the Examination of Water and Wastewater:

Accuracy: estimate of how close a measured value is to the true value; includes expressions for bias and precision.

Precision: a measure of the degree of agreement among replicate analyses of a sample.

A reputable laboratory will measure the Accuracy and Precision of QC samples in a batch of user samples and record these values in both the analytical test report issued to the user and in control charts kept by the laboratory. These control charts can be reviewed by the user if they are requested by the user. These control charts record:

Accuracy (means) chart: The accuracy chart for QC samples (e.g., LRB, CCV, LFBs, LFMs, and surrogates) is constructed from the average and standard deviation of a specified number of measurements of the analyte of interest.

Precision (range) chart: The precision chart also is constructed from the average and standard deviation of a specified number of measurements (e.g., %RSD or RPD) for replicate of duplicate analyses of the analyte of interest.

Now, let’s look at what should be run in a sample batch for cannabis analyses. The typical cannabis sample would have analyses for cannabinoids, terpenes, microbiological, organic compounds, pesticides and heavy metals.

Each compound listed above would require a specific validated analytical method for the type of matrix being analyzed. Examples of specific matrixes are:

  • Cannabis buds, leaves, oil
  • Edibles, such as Chocolates, Baked Goods, Gummies, Candies and Lozenges, etc.
  • Vaping liquids
  • Tinctures
  • Topicals, such as lotions, creams, etc.

Running QC analyses does not guarantee that the user’s specific sample in the batch was analyzed correctly.

Also, both ISO 17025-2005 and ISO 17025-2017 require the use of a validated method.

ISO 17025-2005: When it is necessary to use methods not covered by standard methods, these shall be subject to agreement with the customer and shall include a clear specification of the customer’s requirements and the purpose of the test and/or calibration. The method developed shall have been validated appropriately before use.

ISO 17025-2017: The laboratory shall validate non-standard methods, laboratory-developed methods and standard methods used outside their intended scope or otherwise modified. The validation shall be as extensive as is necessary to meet the needs of the given application or field of application.

Validation procedures can be found in a diverse number of analytical chemistry associations (such as AOACand ASTM) but the State of California has directed users and laboratories to the FDA manual “Guidelines for the Validation of Chemical Methods for the FDA FVM Program, 2nd Edition, 2015”

The laboratory must have on file for user review the following minimum results in an analytical statistical report validating their method:

  • accuracy,
  • limit of quantitation,
  • ruggedness,
  • precision,The user must look beyond the QC data provided in their analytical report or laboratory control charts.
  • linearity (or other calibration model),
  • confirmation of identity
  • selectivity,
  • range,
  • spike recovery.
  • limit of detection,
  • measurement uncertainty,

The interpretation of an analytical statistical report will be discussed in detail in the next article. Once the validated method has been selected for the specific matrix, then a sample batch is prepared for analysis.

Sample Batch: A sample batch is defined as a minimum of one (1) to a maximum of twenty (20) analytical samples run during a normal analyst’s daily shift. A LRB, LFB, LFM, LFMD, and CCV will be run with each sample batch. Failure of any QC sample in sample batch will require a corrective action and may require the sample batch to be reanalyzed. The definitions of the specific QC samples are described later.

The typical sample batch would be set as:

  • Instrument Start Up
  • Calibration zero
  • Calibration Standards, Quadratic
  • LRB
  • LFB
  • Sample used for LFM/LFMD
  • LFM
  • LFMD
  • Samples (First half of batch)
  • CCV
  • Samples (Second half of batch)
  • CCV

The QC samples are defined as:

Calibration Blank: A volume of reagent water acidified with the same acid matrix as in the calibration standards. The calibration blank is a zero standard and is used to calibrate the ammonia analyzer

Continuing Calibration Verification (CCV): A calibration standard, which is analyzed periodically to verify the accuracy of the existing calibration for those analytes.

Calibration Standard: A solution prepared from the dilution of stock standard solutions. These solutions are used to calibrate the instrument response with respect to analyte concentration

Laboratory Fortified Blank (LFB): An aliquot of reagent water or other blank matrix to which known quantities of the method analytes and all the preservation compounds are added. The LFB is processed and analyzed exactly like a sample, and its purpose is to determine whether the methodology is in control, and whether the laboratory is capable of making accurate and precise measurements.

Laboratory Fortified Sample Matrix/Duplicate (LFM/LFMD) also called Matrix Spike/Matrix Spike Duplicate (MS/MSD): An aliquot of an environmental sample to which known quantities of ammonia is added in the laboratory. The LFM is analyzed exactly like a sample, and its purpose is to determine whether the sample matrix contributes bias to the analytical results. The background concentrations of the analytes in the sample matrix must be determined in a separate aliquot and the measured values in the LFM corrected for background concentrations (Section 9.1.3).Laboratories must validate their methods.

Laboratory Reagent Blank (LRB): A volume of reagent water or other blank matrix that is processed exactly as a sample including exposure to all glassware, equipment, solvents and reagents, sample preservatives, surrogates and internal standards that are used in the extraction and analysis batches. The LRB is used to determine if the method analytes or other interferences are present in the laboratory environment, the reagents, or the apparatus.

Once a sample batch is completed, then some of the QC results are provided in the user’s analytical report and all of the QC results should be recorded in the control charts identified in the accuracy and precision section above.

But having created a batch and performing QC sample analyses, the validity of the user’s analytical results is still not guaranteed. Key conclusion points to consider are:

  1. Laboratories must validate their methods.
  2. Running QC analyses does not guarantee that the user’s specific sample in the batch was analyzed correctly.
  3. QC Charts can provide a detailed overview of laboratory performance in a well-run laboratory.

The user must look beyond the QC data provided in their analytical report or laboratory control charts. Areas to look at will be covered in the next few articles in this series.

Lauren Pahnke
From The Lab

Centrifugal Partition Chromatography Paves the Way for Safer, More Standardized Cannabidiol Drugs

By Lauren Pahnke
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Lauren Pahnke

Imagine this: you are taking medication for cancer pain. One day, it works perfectly. The next, you feel no relief. On some days, you need to take three doses just to get the same effect as one. Your doctor can’t be completely positive how much active ingredient each dose contains, so you decide for yourself how much medication to take.

Doesn’t seem safe, right? It is crucial that doctors know exactly what they are prescribing to their patients. They must know that their patients are receiving the exact same dose of medication in their prescription each time they take it, and that their medication contains only the intended ingredients.

consistency is key to creating products that are safe for consumers.In the cannabis industry, lack of certainty on these important factors is a major problem for drug manufacturers as they attempt to incorporate cannabidiol (CBD), a compound found in cannabis that has no psychoactive effects but many medical benefits, into pharmaceutical drugs.

When using these compounds as medications, purity is essential. Cannabis contains a wide variety of compounds. Delta-9 tetrahydrocannabinol (THC) is the most well-known compound and its main psychoactive one1. Safety regulations dictate that consumers know exactly what they are getting when they take a medication. For example, their CBD-based medications should not contain traces of THC.

The cannabis industry greatly needs a tool to ensure the consistent extraction and isolation of compounds. In 2017, the cannabis industry was worth nearly $10 billion, and it is expected to grow $57 billion more in the next decade2. As legalization of medical cannabis expands, interest in CBD pharmaceuticals is likely to grow.

If compounds such as CBD are going to be used in pharmaceutical drugs, consistency is key to creating products that are safe for consumers.

CBD’s Potential

CBD is a non-psychoactive compound that makes up 40 percent of cannabis extracts1. It is great for medical applications because it does not interfere with motor or psychological function. Researchers have found it particularly effective for managing cancer pain, spasticity in multiple sclerosis, and specific forms of epilepsy3.

Figure 1: The chemical structure of cannabidiol.
Figure 1: The chemical structure of cannabidiol.

Other compounds derived from cannabis, such as cannabichromene (CBC) and cannabigerol (CBG), may also be beneficial compounds with medical applications. CBC is known to block pain and inflammation, and CBG is known for its use as a potential anti-cancer agent1.

Along with these compounds that provide medical benefits, there are psychoactive compounds that are used recreationally, such as THC.

“It will definitely be an advantage to have cannabis-based medications with clearly defined and constant contents of cannabinoids,” says Kirsten Müller-Vahl, a neurologist and psychiatrist at Hannover Medical School in Germany.

Creating a Standard Through Centrifugal Partition Chromatography

To obtain purified compounds from cannabis, researchers need to use technology that will extract the compounds from the plant.

Many manufacturers use some sort of chromatography technique to isolate compounds. Two popular methods are high performance liquid chromatography (HPLC) and flash chromatography. These methods have their places in the field, but they cannot be effectively and cost-efficiently scaled to isolate compounds. Instead, HPLC and flash chromatography may be better suited as analytical tools for studying the characteristics of the plant or extract. As cannabis has more than 400 chemical entities4, compound isolation is an important application.

This method is highly effective for achieving both high purity and recovery.Although molecules such as CBD can be synthesized in the lab, many companies would rather extract the compounds directly from the plant. Synthesized molecules do not result in a completely pure compound. The result, “is still a mixture of whatever cannabinoids are coming from a particular marijuana strain, which is highly variable,” says Brian Reid, chief scientific officer of ebbu, a company in Colorado that specializes in cannabis purification.

Currently, there is only one method available to researchers that completely allows them to isolate individual compounds: centrifugal partition chromatography (CPC).

The principle of CPC is similar to other liquid chromatography methods. It separates the chemical substances as the compounds in the mobile phase flow through and differentially interact with the stationary phase.

Where CPC and standard liquid chromatography differs is the nature of the stationary phase. In traditional chromatography methods, the stationary phase is made of silica or other solid particles, and the mobile phase is made of liquid. During CPC, the stationary phase is a liquid that is spun around or centrifuged to stay in place while the other liquid (mobile phase) moves through the disc. The two liquid phases, like oil and water, don’t mix. This method is highly effective for achieving both high purity and recovery. Chemists can isolate chemical components at 99 percent or higher purity with a 95 percent recovery rate5.

“CPC is ideal for ripping a single active ingredient out of a pretty complex mixture,” says Reid. “It’s the only chromatographic technique that does that well.”

The Need for Pure Compounds

High levels of purity and isolation are necessary for cannabis to be of true value in the pharmaceutical industry. Imagine relying on a medication to decrease your seizures, and it has a different effect every time. Sometimes there may be traces of psychoactive compounds. Sometimes there are too much or too little of the compound that halts your seizures. This is not a safe practice for consumers who rely on medications.“It’s hard to do studies on things you can’t control very well.”

Researchers working with cannabis desperately need a technology that can extract compounds with high purity rates. It is hard to run a study without knowing the precise amounts of compounds used. Reid uses a Gilson CPC 1000 system at ebbu for his cannabinoid research. With this technology, he can purify cannabinoids for his research and create reliable formulations. “Now that we have this methodology dialed in we can make various formulations —whether they’re water-soluble, sublingual, inhaled, you name it —with very precise ratios of cannabinoids and precise amounts of cannabinoids at the milligram level,” says Reid.

Kyle Geary, an internist at the University of Illinois at Chicago, is currently running a placebo-controlled trial of CBD capsules for Crohn’s disease. This consistent isolation is helpful for his research, as well. “Ideally, the perfect study would use something that is 100 percent CBD,” says Geary. “It’s hard to do studies on things you can’t control very well.”

The State of the Industry

While CBD is not considered a safe drug compound under federal law in the United States6, 17 states have recently passed laws that allow people to consume CBD for medical reasons7. Half of medicinal CBD users solely use the substance for treatment, a recent survey found8. As the industry quickly grows, it is crucial that consumer safety protocol keeps pace.

In June, the US Food and Drug Administration (FDA) approved the first drug that contains a purified drug substance from cannabis, Epidiolex9. Made from CBD, it is designed to treat Dravet Syndrome and Lennox-Gastaut syndrome, two rare forms of epilepsy. FDA Commissioner Scott Gottlieb said in the news release that although the FDA will work to support the development of high-quality cannabis-based products moving forward, “We are prepared to take action when we see the illegal marketing of CBD-containing products with serious, unproven medical claims. Marketing unapproved products, with uncertain dosages and formulations can keep patients from accessing appropriate, recognized therapies to treat serious and even fatal diseases.”

The industry should be prepared to implement protocols to ensure the quality of their CBD-based products. The FDA has issued warnings in recent years that some cannabinoid products it has tested do not contain the CBD levels their makers claim, and consumers should be wary of such products10. It’s hard to know when or if the FDA will begin regulating CBD-based pharmaceuticals. However, for pharma companies serious about their reputation, there is only one isolation method that creates reliable product quality: CPC.

References:

  1. Lab Manager. (2018, January 3). Cannabinoid Chemistry Infographic. Retrieved from http://www.labmanager.com/multimedia/2017/07/cannabinoid-chemistry-infographic#.WzT2e1MvyMI
  2. BDS Analytics. (2018, February 26). NEW REPORT: Worldwide spending on legal cannabis will reach $57 billion by 2027. Retrieved from https://bdsanalytics.com/press/new-report-worldwide-spending-on-legal-cannabis-will-reach-57-billion-by-2027/
  3. National Institute on Drug Abuse. (2015, June 24). The Biology and Potential Therapeutic Effects of Cannabidiol. Retrieved from https://www.drugabuse.gov/about-nida/legislative-activities/testimony-to-congress/2016/biology-potential-therapeutic-effects-cannabidiol
  4. Atakan, Z. (2012). Cannabis, a complex plant: Different compounds and different effects on individuals. Therapeutic Advances in Psychopharmacology,2(6), 241-254. doi:10.1177/2045125312457586
  5. Gilson. (n.d.). Centrifugal Partition Chromatography (CPC) Systems. Retrieved from http://www.gilson.com/en/AI/Products/80.320#.WzVB2lMvyMI
  6. Mead, A. (2017). The legal status of cannabis (marijuana) and cannabidiol (CBD) under US law. Epilepsy & Behavior, 70, 288-291.
  7. ProCon.org. (2018, May 8). 17 States with Laws Specifically about Legal Cannabidiol (CBD) – Medical Marijuana – ProCon.org. Retrieved from https://medicalmarijuana.procon.org/view.resource.php?resourceID=006473
  8. Borchardt, D. (2017, August 03). Survey: Nearly Half Of People Who Use Cannabidiol Products Stop Taking Traditional Medicines. Retrieved from https://www.forbes.com/sites/debraborchardt/2017/08/02/people-who-use-cannabis-cbd-products-stop-taking-traditional-medicines/#43889c942817
  9. U.S. Food & Drug Administration. (2018, June 25). Press Announcements – FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy. Retrieved from https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm611046.htm
  10. U.S. Food & Drug Administration. (2017). Public Health Focus – Warning Letters and Test Results for Cannabidiol-Related Products. Retrieved from https://www.fda.gov/newsevents/publichealthfocus/ucm484109.htm
Rob Adelson
Soapbox

Collaborative Health Model to Advance Cannabis Research

By Rob Adelson
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Rob Adelson

The projected growth of the legal cannabis market is astounding. According to a report from BDS Analytics, the industry is expected to grow from $9.2B to $47.3B in 2027 in North America, with medical cannabis contributing 33% of that overall growth. While this number is impressive for an industry still in its infancy, I have reason to believe it can be much higher.

In the pharmaceutical industry, treatment of pain and insomnia represent an annual revenue exceeding $140B; concurrently, studies have shown cannabis to be an effective treatment for both conditions. If medical cannabis can capture 10% of that revenue over the next ten years, it essentially doubles the current estimates mentioned above.

So, what stands in our way? Education.

To gain acceptance from the medical community, physicians need to better understand the plant and its therapeutic benefits. To do so, they need more substantial data to prove cannabis’ efficacy before prescribing it to their patients. However, federal illegalities have prevented government-mandated clinical studies, but I believe there’s another way.

By adopting a collaborative health care model, patients and caregivers can work together to track the effectiveness of their cannabis treatments and share their learnings with the larger medical community.  With the right tools in place, we can fast-track the research process and provide physicians and politicians with the information they need to make this medicine more approachable and accessible to those who could benefit from it.

By harnessing the power of the community, we can apply learnings from one patient’s cannabis use to help countless others.The Spine Patient Outcomes Research Trial (SPORT) was a five-year study consisting of approximately 2500 patients with back and spine conditions. Participants entered qualitative data into an online portal, including post-surgical results and patient outcomes, to provide a comprehensive insight into treatment methods and their efficacy. Today, others suffering with those same conditions can enter their personal information into an online calculator and receive a prospective treatment plan. Together, patients and their doctors can view results and build a customized plan using more informed decisions about the available treatment options.

Another example comes from OpenNotes– an exploratory study that provides patients with full access to their medical files and the opportunity to input comments about their doctor visits and prognosis and make corrections related to the care they received. Results showed that this process helped patients retain a better understanding of their condition which improved their decision making and resulted in increased adherence to treatment plan protocols because they had greater trust with their doctors.Not only will this improve the patient experience by providing a safer, more sustainable treatment option, it also provides a very significant financial opportunity.

I believe the cannabis industry can take a leadership role in empowering patients to become active participants in their own treatment, while also sharing knowledge with the larger patient and physician communities. In fact, this core belief was the reason I founded Resolve Digital Health. Data-empowered patients not only make better decisions but also enjoy a greater feeling of control over their treatment. The power of collaborative healthcare grows exponentially when the data is shared to educate a broader group. By harnessing the power of the community, we can apply learnings from one patient’s cannabis use to help countless others.

Businesses within the cannabis industry can also leverage this data to create new products and services. For example, insights as to what products work best for certain conditions can help LP’s improve their product offerings and guide recommendations from dispensaries. Through product innovation, companies can make cannabis more accessible to a larger group of patients, who may be currently taking pharmaceuticals. Not only will this improve the patient experience by providing a safer, more sustainable treatment option, it also provides a very significant financial opportunity.

Ultimately, knowledge is power. When patients are empowered to make educated decisions about their health care and doctors are more tuned into the patient-tested cannabis treatment options, it’s a win-win for everyone.