Tag Archives: 3M

From MedTech to Cannabis: A Q&A with Jennifer Raeder-Devens

By Aaron G. Biros
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Project Yosemite, a cannabis product innovation and brand development company, announced earlier this month the appointment of Jennifer Raeder-Devens as their new Chief Scientific Officer. Raeder-Devens is a veteran of the MedTech industry, working for companies like Becton Dickinson, Cardinal Health, Medtronic and 3M.

Prior to joining Yosemite, she was the Vice President of Research & Development at Becton, Dickinson, where she oversaw product development and technology strategies to launch infection prevention products including the ChloraPrep first-in-the-US sterile solution patient preoperative topical antiseptic. She was previously the Vice President of R&D, Strategy and Innovation at Cardinal Health. She’s also held roles at Medtronic, 3M Drug Delivery Systems and 3M Skin Health Division and she has a number of patents in drug delivery and medical devices.

Jennifer Raeder-Devens, Chief Scientific Officer at Project Yosemite

In November of 2018, Project Yosemite launched their first product, OLO, which is an infused, controlled-release sublingual strip. Part of Raeder-Devens’ new role at the company is the continued development and expansion of the OLO sublingual strip technology platform. Andrew Mack, CEO and founder of Project Yosemite, says he’s thrilled to have Raeder-Devens on the team. “Jennifer is an extremely accomplished scientist and engineer with extensive experience driving innovation and R&D in the pharmaceutical and medical device industries,” says Mack.

We caught up with Jennifer over the phone to talk about her background in the MedTech space, why she decided to jump ship to join the cannabis industry and what she’s excited to work on now.

Cannabis Industry Journal: Can you tell us about your background, including your work with 3M and Medtronic? 

Jennifer Raeder-Devens: I’m coming directly from Becton Dickinson, a global med tech company, where I supervised the development of drug-device combination products for topical antiseptics. I spent about 10 years there, mostly in topical drug and combination product development. Prior to that, I was at 3M and Medtronic working in drug-device combination products. At 3M, I was supervising a team of technology developers for the 3M Drug Delivery Systems business. I had experience working with designing and manufacturing transdermal, nasal, buccal and inhalation drug delivery mechanisms for pharmaceutical partners.

I worked on implantable drug delivery systems at Medtronic, which included working on the biocompatibility of things like pacemakers and drug infusion pumps and optimizing them to reduce infection and enhance healing after the implantation procedure.

CIJ: What made you consider joining the cannabis industry? 

Jennifer: With my work in topicals, transdermal and inhalation drug delivery, I had an easy understanding of the different routes of administration we see today in the cannabis industry. And so, from the technology standpoint, I thought this was a place I could contribute to immediately. And then what got me really excited about it was thinking about cannabis, and just like any other drug, with oral drug delivery, you’ve got first class metabolism and side effects from the 11-Hydroxy-THC that are undesirable and you’d rather not have delivered through the gut.

OLO sublingual strips have a 10-minute onset time

I got excited when I saw the development of things like sublingual strips that were focusing on alternatives to smoking that would preserve that relatively fast onset and mitigate some of the side effects of edibles.

The other thing I really like about the cannabis industry: Previously I have been very focused on known drugs that are already approved and repurposing them into a new delivery system. What really interests me about the cannabis industry is the active cannabinoids and terpenes are somewhat known and somewhat unknown, so there is this really interesting challenge there of trying to separate the wheat from the chaff in terms of producing therapeutic effects.

It is a really interesting space where the indications of certain molecules are evolving along with the delivery technology. So, it is a really exciting and eye-opening way to take the next step in my career and have this wide-open space in front of me, both in terms of the different cannabinoids, their effects and the delivery systems we can use.

CIJ: How might you be prepared, given your background, for some of the challenges in the cannabis space?

Jennifer: I think the challenges in cannabis delivery are not different from the challenges in pharmaceutical drug delivery. It’s just that we have this additional complexity of the entourage effect. We can be engineering not just the main ingredient of THC, but also all the other cannabinoids and terpenes. So, for example, with my background in infection prevention, we build a product that we know reduces the risk of infection, but we are really challenged to actually prove it reduces the risk of infection. We have a similar situation in the cannabis industry, where we can get the THC, or CBG or CBN where we want it to go, but then we are really challenged to figure out how we can find, what we call in the pharmaceutical industry, a surrogate end point for efficacy, so that we can test that product and really believe that when we put the product on the market, even though we haven’t tested thousands of users or conducted large randomized clinical trials, that the effect will be shown. We are networking and partnering with a good scientific community to build the right product and do some testing at a small scale that really demonstrates the product achieves the effect that we are really looking for.

CIJ: Can you tell us a little about your new role with Project Yosemite?

Jennifer: My job description falls into three buckets: The first part is that we are forming a scientific advisory board and we are working with some of the leading cannabinoid researchers around the country and around the world. These are the people identifying whether or not certain cannabinoids could reduce cancer cell metabolism or whether cannabinoids contribute to weight loss or diabetes control and other things of that nature. We are trying to reach as far upstream as we can to grasp the emerging understanding of the performance of cannabinoids and terpenes in the endocannabinoid system. So, part of my job is to chair that scientific advisory board, get the thought leaders together in the room and have them bring their knowledge and explore with our own knowledge what cannabis can really do.

The OLO sublingual strips

I have worked in topical, transdermal, buccal, nasal, inhalation drug delivery. In the second bucket of my job, we are trying to understand a given indication or experience that our users want to have, what would be the right route for them. We are challenging our sublingual delivery mechanism to see how fast of an onset we can really get. Right now, we are at 10 minutes for drug delivery in sublingual and we are still trying to get an even faster onset time for the sublingual strip.

For other indications, like chronic pain, we may want to think about a sustained release, so sort of aligning the different indications with which different cannabinoids and terpenes will work for it and see which delivery platform will work for what we are trying to accomplish in each indication.  So, we do not plan to remain solely a sublingual strip company, but will build out additional delivery platforms as we develop new indications.

Right now, we are working upstream with the growers and the processors to get cannabis oil and extracts. Some of the growers are working on different genetics in their cultivars to grow plants that have different ratios of different cannabinoids that we know from the emerging research will have an impact on people’s experience. Now we are working with growers to really get ahead of the curve on how to formulate products with various cannabinoids.

We have an R&D team in house that I supervise. We are always working with our production team to make small improvements such as the faster onset and the dissolution rate and things like flavors, which covers a downstream focus as well.

3 Essential Components of Microbial Safety Testing

By Heather Ebling
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Microbial contamination on cannabis products represents one of the most significant threats to cannabis consumers, particularly immunocompromised patients who are at risk of developing harmful and potentially fatal infections.

As a result, regulatory bodies in the United States and Canada mandate testing cannabis products for certain microbes. The two most popular methods for microbial safety testing in the cannabis industry are culture-based testing and quantitative polymerase chain reaction (qPCR).

When considering patient safety, labs should choose a method that provides an accurate account of what is living on the sample and can specifically target the most harmful microbes, regardless of the matrix.

1. The Method’s Results Must Accurately Reflect the Microbial Population on the Sample

The main objective of any microbial safety test is to give the operator an indication of the microbial population present on the sample.

Figure 1: MA data collected directly from plant material before and after culture on 3M petrifilm and culture-based platforms.

Culture-based methods measure contamination by observing how many organisms grow in a given medium. However, not all microbial organisms grow at the same rate. In some cases, certain organisms will out-compete others and as a result, the population in a post-culture environment is radically different than what was on the original sample.

One study analyzed fifteen medicinal cannabis samples using two commercially available culture-based methods. To enumerate and differentiate bacteria and fungi present before and after growth on culture-based media, all samples were further subjected to next-generation sequencing (NGS) and metagenomic analyses (MA). Figure 1 illustrates MA data collected directly from plant material before and after culture on 3M petrifilm and culture-based platforms.

The results demonstrate substantial shifts in bacterial and fungal growth after culturing on the 3M petrifilm and culture-based platforms. Thus, the final composition of microbes after culturing is markedly different from the starting sample. Most concerning is the frequent identification of bacterial species in systems designed for the exclusive quantification of yeast and mold, as quantified by elevated total aerobic count (TAC) Cq values after culture in the total yeast and mold (TYM) medium. The presence of bacterial colonies on TYM growth plates or cartridges may falsely increase the rejection rate of cannabis samples for fungal contamination. These observations call into question the specificity claims of these platforms.

The Live Dead Problem

Figure 2: The enzyme is instantaneously inactivated when lysis buffer is added

One of the common objections to using qPCR for microbial safety testing is the fact that the method does not distinguish between live and dead DNA. PCR primers and probes will amplify any DNA in the sample that matches the target sequence, regardless of viability. Critics claim that this can lead to false positives because DNA from non-viable organisms can inflate results. This is often called the Live-Dead problem. However, scientists have developed multiple solutions to this problem. Most recently, Medicinal Genomics developed the Grim Reefer Free DNA Removal Kit, which eliminates free DNA contained in a sample by simply adding an enzyme and buffer and incubating for 10 minutes. The enzyme is instantaneously inactivated when lysis buffer is added, which prevents the Grim Reefer Enzyme from eliminating DNA when the viable cells are lysed (see Figure 2).

2. Method Must Be Able to Detect Specific Harmful Species 

Toxic Aspergillus spp., which is responsible for at least one confirmed death of a cannabis patient, grows poorly in culture mediums and is severely underreported by current culture-based platforms. And even when Aspergillus does grow in culture, there is a certain non-pathogenic Aspergillus species that look remarkably similar to their pathogenic cousins, making it difficult to speciate using visual identification alone.

Figure 3: The team spiked a known amount of live E. coli into three different environments

Conversely, qPCR assays, such as the PathoSEEK, are designed to target DNA sequences that are unique to pathogenic Aspergillus species, and they can be run using standard qPCR instruments such as the Agilent AriaMx. The primers are so specific that a single DNA base difference in the sequence can determine whether binding occurs. This specificity reduces the frequency of false positives in pathogen detection, a frequent problem with culture-based cannabis testing methods.

Additionally, Medicinal Genomics has developed a multiplex assay that can detect the four pathogenic species of Aspergillus (A. flavus, A. fumigatus, A. niger, and A. terreus) in a single reaction.

3. The Method Must Work on Multiple Matrices 

Figure 4: The team also placed TSB without any E. coli onto a petrifilm to serve as a control.

Marijuana infused products (MIPs) are a very diverse class of matrices that behave very differently than cannabis flowers. Gummy bears, chocolates, oils and tinctures all present different challenges to culture-based techniques as the sugars and carbohydrates can radically alter the carbon sources available for growth. To assess the impact of MIPs on colony-forming units per gram of sample (CFU/g) enumeration, The Medicinal Genomics team spiked a known amount of live E. coli into three different environments: tryptic soy broth (TSB), hemp oil and hard candy. The team then homogenized the samples, pipetted amounts from each onto 3M™ Petrifilm E. coli / Coliform Count (EC) Plates, and incubated for 96 hours. The team also placed TSB without any E. coli onto a petrifilm to serve as a control. Figures 3 and 4 show the results in 24-hour intervals.

Table 1: DNA was spiked into various MIPs

This implies the MIPs are interfering with the reporter assay on the films or that the MIPs are antiseptic in nature.

Many MIPs use citric acid as a flavoring ingredient which may interfere with 3M reporter chemistry. In contrast, the qPCR signal from the Agilent AriaMx was constant, implying there is microbial contamination present on the films, but the colony formation or reporting is inhibited.

Table 3: SenSATIVAx DNA extraction can successfully lyse the cells of the microbes
Table 2: Different numbers of DNA copies spiked into chocolate

This is not an issue with DNA-based methods, so long as the DNA extraction method has been validated on these matrices. For example, the SenSATIVAx DNA extraction method is efficient in different matrices, DNA was spiked into various MIPs as shown in Table 1, and at different numbers of DNA copies into chocolate (Table 2). The SenSATIVAx DNA extraction kit successfully captures the varying levels of DNA, and the PathoSEEK detection assay can successfully detect that range of DNA. Table 3 demonstrates that SenSATIVAx DNA extraction can successfully lyse the cells of the microbes that may be present on cannabis for a variety of organisms spiked onto cannabis flower samples.

Colorado Cannabis Lab Methods Updated for Microbial Testing

By Aaron G. Biros
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The Colorado Department of Public Health and Environment’s (CDPHE) Marijuana Laboratory Inspection Program issued a bulletin on January 30th regarding updates required for licensed cannabis testing labs. The updated method for microbial contaminant testing includes a longer incubation period in yeast and mold testing.BannerForEnf

“After careful consideration of emerging data regarding the use and effectiveness of 3M Total Yeast and Mold Rapid Petrifilms in marijuana, CDPHE has concluded that 48 hours is not a sufficient incubation period to obtain accurate results,” the letter states. “Based upon the review of this information, marijuana/marijuana products require 60-72 hours of incubation as per the manufacturer’s product instructions for human food products, animal feed and environmental products.” The letter says they determined it was necessary to increase the incubation period based on data submitted from several labs, along with a paper found in the Journal of Food Protection.

An incubator (Right) at TEQ Analytical Labs
An incubator (Right) at TEQ Analytical Labs

According to Alexandra Tudor, manager of the microbiology department at TEQ Analytical Labs (a cannabis testing lab in Aurora, CO), the update is absolutely necessary. “The incubation time extension requirement from CDPHE offers more reliable and robust data to clients by ruling out the possibility of a false yeast and mold result during analysis,” says Tudor.

Alexandra Tudor, microbiology department manager at TEQ Analytical Labs
Alexandra Tudor, microbiology department manager at TEQ Analytical Labs

“3M, the maker of Petrifilm, recommends an incubation time of 48-72 hours, but during TEQ’s method validation procedure, we learned that 48-hour incubation was not sufficient time to ensure accurate results. Although some laboratories in industry had been incubating for the minimum amount of time recommended by the manufacturer, the 48-hour incubation time does not provide a long enough window to ensure accurate detection of microbiological contaminants present in the sample.” Tudor says the update will help labs provide more confident results to clients, promoting public health sand safety.IMG_6386-2

As a result of the update in testing methodology, cultivators and infused product manufacturers in Colorado need to submit a batch test for yeast and mold. The point of requiring this batch test is to determine if the producer’s process validation is still effective, given the new yeast and mold testing method.