2019 canna-pharma program · canna-pharma 2019 advancing the science of medicinal cannabis through...

PharmaEd Resources, Inc. • 2810 Robeson Park Drive • Champaign, IL 61822tel. 217.721.5774 • web. www.pharmaedresources.com

Canna-Pharma 2019Advancing the Science of Medicinal Cannabis Through

GMP, Quality Control, & Regulatory ComplianceNovember 13 –14, 2019, Marriott Mission Valley, San Diego CA

Featuring Lessons Learned and Case Studies from Industry Experts:

With Comprehensive Coverage On:

With Representation From:

• Challenges in Creating Standards for Quality Control of Cannabis Derived Products

• Updates from Industry Working Groups: ASTM D37, AHPA, USP, & AOAC International

• Analytical Testing Strategies for Pesticides, Trace Metals & Other Contaminants

• Regulatory Panel Discussion—Hear from the Experts

• Cannabis Genetics: The Path to Better Medicinal Cannabis

• Hot Topics in Therapeutic Cannabis Research

• Key Formulation Considerations for Improved Bioavailability of Cannabinoids

• Evaluating the Volatile Constituents of Different Cannabis Varieties using Various Sample Preparation Approaches, and Mass Spec Detection

• Environmental Monitoring for GMP Compliance in Grow Facilities

• Cannabis Microbiome Sequencing: Implications for Cannabis Safety Testing

• Cleaning Validation and GMPs for Medicinal Cannabis Products

• The Therapeutic Potential of Cannabinoid Medicines Applied on the Skin

• Intellectual Property Considerations for Medical Cannabis

• And Much More!

Wayne Nasby (Event Chair)Ocean Grown

Ventures

Heather Despres

Americans for Safe Access

Ralph ParoliNational

Research Council of Canada

Reggie GaudinoFront Range Biosciences

Ethan Russo

ICCI

Brad Douglass

The Werc Shop

Audra Stinchcomb

University of Maryland

Jeffrey Raber

The Werc Shop

Jasmine Musakhanian

Gattefossè

Matthew EdwardsSepSolve Analytical

Charlotte Peyton

EAS Consulting Group

Marc StegemanPro Pharma

Group

Anthony Macherone

Agilent Technologies

Beth Kroeger

Steris

Michael Moussourakis

Alconox

Andrea Small-Howard

GBS Global Biopharma

Robert Morgan

ASTM

Susan Audino

AOAC International

Zarha RuizMCSB, CA Dept. of Public Health

Lori DodsonMD Medical

Cannabis Comm.

Heather KrugCO Dept. of Public

Health

Holly JohnsonAHPA/USP

Parithosh Tungaturthi

LexKannabis, LLC

Theo Kapanadze

Diteba

Gyorgy VasVas Analytical

Diane GleinserUSDM Life Sciences

Kevin McKernan

Medicinal Genomics

James BrennanLabWare

Erin Northington

USDM Life Sciences

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Canna-Pharma 2019

product quality. The proliferation of an enormous variety of delivery vehicles in the market also presents chal-lenges in matrix extension validation for standard test methods. This talk will discuss initiatives to create use-ful and rigorous quality standards for industry, including the United States Pharmacopeia’s Expert Panel on Med-ical Cannabis and AOAC’s Cannabis Analytical Science Program, and explore the challenges of developing fit for purpose validated analytical methods that are applicable broadly among US states and internationally with a myr-iad of often incongruent regulations.

9:30 Cannabis Testing in a Rapidly Changing IndustryDr. Susan Audino, Chair, Cannabis Advisory Panel and Chair, Cannabis Working Group, AOAC International

In a rapidly changing industry, regulatory bodies, product manufactures, and scientists strive to provide

cannabis consumers with safe products with known con-centrations of constituents of interest. Although canna-bis cultivators and product manufacturers may conduct in-house testing to ascertain the status of product devel-opment, all parties look to the external third-party testing labs to provide empirical data that attests to the veracity of the statements made about the final product.

These third-party analytical testing laboratories must rely on solid scientific processes and technologies to yield sound results accurately and precisely. Relying on laboratory accreditation to the pinnacle international standard of laboratory quality that is ISO/IEC 17025, lab-oratories are compelled to develop analytical test meth-ods that are based using appropriate technology and competence to build methods that are well characterized to a number of parameters as well as forming a determi-nation of measurement uncertainties.

This session will discuss progress chemists have made to the development of standard test methods with the as-sistance of international scientific organizations. Specif-ically, participants will leave with a list of test methods established by cannabis working groups in AOAC Inter-national and ASTM International, in particular.

10:00 Quality Control & Analytical Testing: Achieving Standardization

Moderator: Chair Wayne Nasby

Panelists: Ralph Paroli, Holly Johnson, Susan Audino

Participants: The Audience

10:30 Morning Coffee & Networking Break

Wednesday, November 13

7:45 Complimentary Breakfast

8:25 Opening Remarks from Chairperson

Wayne Nasby, COO, Ocean Grown Ventures

Critical Issues—Spotlight on Quality Control and Analytical Testing Standards for the Medicinal Cannabis Industry

8:30 Developing Normative Standards at ASTM International

Dr. Ralph M. Paroli, Director, R&D, National Research Council of Canada and Robert J. Morgan, Director, ASTM International

Standard developing organizations (SDOs) such as ASTM International develop product safety standards using the consensus process. This, of course, gives everyone an equal voice in the process. The purpose of these voluntary standards is to help enhance safety and performance. The standards help enhance safety because it provides regulators with tools to develop

laws and regulations to ensure that the products we are consuming are tested or analyzed with confidence using methods which have appropriate certification, calibration, etc. For example, pesticide presence needs to be mea-sured accurately so that the levels allowed by regulators are within the appropriate tolerances. This presentation will provide an update on what has been accomplished at ASTM International Committee D37 in the areas of: Indoor and Outdoor Horticulture and Agriculture; Quality Man-agement Systems; Laboratory; Processing and Handling; Security and Transportation; Personnel Training, Assess-ment, Credentialing; and Industrial Hemp.

9:00 Challenges in Creating Standards for Quality Control of Cannabis Derived Products

Holly E. Johnson, Ph.D., Chief Science Officer, American Herbal Products Association, & Member, USP Expert Panel on Medical Cannabis

Cannabis derived natural products for oral delivery, especially medicinal preparations and dietary supple-ments, are steadily gaining popularity with consumers and practitioners. While there is some optimism about the current efforts to clarify the legal status of some such products in the US, the pervading legal and regulatory uncertainty has led to technical challenges in assuring


Canna-Pharma 2019

1:25 Laboratory Informatics for Medicinal Cannabis: Lessons from the Pharmaceutical Industry

James Brennan, Technical Sales Specialist, LabWare, Inc.

The success of the pharmaceutical industry is based, in part, on well-defined processes throughout the en-tire product life cycle, supported by modern and robust

informatics. Pharmaceutical laboratories rely on many data management systems to maintain data integrity and regulatory compliance, from instrument data acquisition to laboratory information management systems, electron-ic lab notebooks, and other software solutions. Cannabis laboratories should consider the implementation of a com-prehensive quality systems model based on the decades of experience the pharmaceutical industry has to offer.

Q & A—Ask the Regulators

1:45 Regulatory Panel: The Present & Future of Medicinal Cannabis Regulation

Moderator: Chair Wayne Nasby

Presenters/Panelists:

Zarha Ruiz, Chief of Inspection & Compliance, Manu-factured Cannabis Safety Branch, California Depart-ment of Public Health

Lori Dodson, Deputy Director, Maryland Medical Can-nabis Commission

Heather Krug, State Marijuana Laboratory Sciences Program Manager, Colorado Department of Public Health and Environment

Participants: The Audience

Research Spotlight—New Sample Preparation Techniques

2:25 Comprehensive Chromatography of Terpenes and Terpenoids from Cannabis Samples: Modernizing the Process from Sample Preparation Through to Data Analysis

Matthew Edwards, Business Development Manager, SepSolve Analytical, partnered with Markes International

The classification of terpenes and terpenoids is an im-portant aspect of cannabis analysis. This is due to the

distinctive aroma and flavour that they impart, as well as their contributions to physiological effects and psychoac-tivity. Specific terpene profiles can be engineered by plant breeders in order to give the desired therapeutic effects.

Volatile organic profiling of cannabis samples often requires extensive sample preparation for efficient ex-traction and concentration the target analytes. Con-ventional sample introduction/injection techniques for GC–FID or GC–MS can result in the abundance of import-ant terpenes being over-estimated, due to the co-elution

The Challenges of Regulatory Compliance in a Fragmented Landscape

11:00 The Importance of Regulatory Compliance in a Changing Regulatory Environment

Heather Despres, Director of Patient Focused Certification, Americans for Safe Access

In 1996 California became the first state to allow the use of medical marijuana. Products went largely unregulat-ed and untested until 2015 when the Medical Cannabis

Regulation and Safety Act was passed. This Act created the regulatory framework for cannabis businesses and initiat-ed mandatory testing of finished products. This framework was then utilized when the Adult Use of Marijuana Act passed in 2016 and both adult-use and medical regulations were combined into the Medical and Adult-Use Cannabis Regulation and Safety Act was passed in 2017.

This presentation will discuss the current changes in California state regulations and provide information on how becoming certified through third-party assessment and certification programs can help businesses weather the seemingly constant changes in regulations. By com-paring and contrasting California regulations with other state regulations we will see how different regulations can be between jurisdictions and how compliance certi-fication companies must stay on top of all these changes to ensure continued compliance.

11:30 Keynote Address: Cannabis Product Ingredients: What Interlocking Regulatory Boundaries Make Sense?

Dr. Brad Douglass, VP of Regulatory Affairs, The Werc Shop, & Dr. Jeffrey C. Raber, CEO, The Werc Shop

There is an old FDA axiom that summarizes when a sub-stance is a drug and/or a food, if it can potentially be both: “First a food, always a food. First a drug, never a food.” Such gating details and the compositional definitions of food, dietary supplements, and drugs are instructive to those interested in any cannabis-derived or -inspired products. The reasons are manifold including likely draft

U.S. hemp regulations and, perhaps in the foreseeable future, U.S. federal adult-use marijuana product regulation. We will synthesize the relevant regulatory doctrine before providing a potential road-map for incorporating all cannabis products into the existing landscape while highlighting the role ana-lytical chemistry has to play. Importantly, we will describe why this issue must be collaboratively addressed by all stakeholders—including hemp, marijuana, and pharma—if we hope to succeed any time soon.

12:10 Lunch Break

1:25 Post-Lunch Presentation, Sponsored by

KEY NOTE


Canna-Pharma 2019

Critical Issues—Best Practices in Cleaning Validation for Cannabis GMP

4:05 Cannabis, Keeping it CleanBeth Kroeger, Technical Services Manager, STERIS

As cannabis use becomes more mainstream, there is a growing demand for testing to ensure the safety of not only medical marijuana, but recreational cannabis as well. Both in Canada and the US, strict guidelines have been

imposed on the industry to ensure the final product does not contain significant levels of harmful substances. This presen-tation will provide an overview of the industry from cultiva-tion, harvesting, and extraction along with the industry issues for meeting these requirements at each of these stages.

4:40 Critical Cleaning—The Key to Quality & Safety Michael Moussourakis, Senior Director, Strategic Affairs, Alconox Inc.

Critically clean processing equipment, whether it be labware, glassware, instrumentation, or processing and extraction equipment, is vital. The potency, purity

and quality, essential characteristics of any drug, rely on critically clean surfaces. Cannabis is no different, and in fact, likely more difficult than traditional drug manu-facturing. Waxy, resin, oily and sticky residues abound which can be highly adherent, difficult to emulsify, and just a plain challenge to remove. Strong solvents and harsh chemicals might be a quick answer, for sure. But the wise answer, the innovative answer, are detergents that are not only effective, but end-user safe, aqueous, free-rinsing, interfering residue-free, biodegradable, and without any added dyes, fragrances, brighteners or soft-eners. In other words, maintaining the whole reason why cannabis, and its “natural” state is sought after.

Critical cleaning is defined as when the level of cleaning directly impacts the value of the final product. The can-nabis and related industries certainly apply, and mastery of both the right detergents, for the right applications, right procedures, and right guidance documentation, en-sures the end product is at its highest efficacy possible.

5:15 Networking Reception

Thursday, November 14 7:30 Complimentary breakfast sponsored by

8:20 Practical Implementation of Cannabis Regulations Through FDA Good Manufacturing Practices (GMPs)

Charlotte Peyton, EAS Consulting Group

While FDA regulations for Good Manufacturing Practic-es are fairly certain in Hemp as specified by Congress in The Farm Bill of 2018, the FDA’s role in Marijuana seems less certain. This presentation will focus on the ways

that both types of cannabis business owners can benefit

of similar compounds or oxygenated derivatives result-ing in reduced confidence in data quality.

This study demonstrates the improved performance of conventional techniques (e.g. Headspace and SPME) us-ing trap-based focusing technology (Headspace-trap and SPME-trap). Appropriate sample preparation coupled with two-dimensional gas chromatography with time-of-flight mass spectrometry (GC×GC-TOF MS) provides a powerful analytical approach to cannabis analysis. This enhanced analytical performance allows common co-elutions to be resolved for increased confidence in data quality and more robust profiling of terpenes across different cannabis strains.

3:00 Afternoon Networking Break

3:30 Evaluating the Volatile Constituents of Different Cannabis Strains using Various Sample Preparation Approaches, and Mass Spectrometric Detection

Gyorgy Vas Ph.D., VasAnalytical, Flemington, NJ

The legalization of medicinal and recreational marijua-na in North America requires an urgent need for reliable, accurate and economical analytical methods to control the active and other constituents of the cannabis plant.

In addition to the natural constituents of the plants, trace level contaminants also need to be rigorously controlled.

Cannabis plants and the derived oils contain more than 100 different terpenoids. Terpenes are one of the most abundant class of compounds naturally present in the cannabis plant, and some believe they have therapeutic effect, and they can enhance the effect of the active cannabinoids. However, some of the terpenes are identified as cosmetic allergens.

This presentation will focus on comparing different sol-ventless sample introduction techniques, including SHS, SPME, SPME-Arrow and dynamic head-space (DHS), and Twister HS. The benefit of using high resolution accurate mass technology (HRAM), will be presented and com-pared to the most common unit resolution mass data.

High resolution accurate-mass based detection in combina-tion with various solventless sample preparation techniques is a new concept for the analysis of cannabis varieties. The most conventional approach for the analysis of volatile can-nabis constituents are based on static head-space and liq-uid extraction with direct injection. The solventless sample preparation offers a unique and comprehensive data pack-age, in less time than the solvent based extraction without the disadvantage of solvent interferences. In addition to the solventless sample preparation techniques, the benefit of using an orbitrap based GC-MS system, will be discussed. The high-resolution accurate-mass detection is not only supporting higher confidence of component identification, its unmatched specificity can enhance the detectability of certain target analytes. The developed sample preparation methods are capable for quick and economical characteri-zation of different cannabis strains and providing analytical support to evaluate the final product and identify quickly any related health risk.

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Canna-Pharma 2019

10:30 Cannabis Genetics: The Path to Better Medicinal Cannabis

Reggie Gaudino, Ph.D., VP of Research & Development, Front Range Biosciences

As interest in Cannabis grows, identifying genes and gene networks involved in production of the desired metabolites (cannabinoids and terpenes) as well as

networks necessary to optimize cultivation potential, will become increasingly important as demand for specific me-tabolites or cultivars grows. In addition to the work Steep Hill has done identifying and analyzing cannabinoid and terpene genes, we have also started a systematic analysis of upstream genes in the cannabinoid and terpene metabol-ic networks, and genes related to growth, development and oil production. Recent advances in reference to genome availability have allowed us to identify and map novel genes and begin the process of metabolic network annota-tion and SNP identification. SNPs identified in the genes of interest are screened using a panel of known cultivars to identify any potential informative regions associated with one or more SNPs. Informative regions are then further as-sessed for their level of informativeness by comparison to chemical or other phenotypic data where available. The combined process contributes to a database that, using the correct methodology, provides a proxy for sequence infor-mation, and where applicable, functional outcome. This in-formation can be used to screen for new cultivars, or breed for specific cultivars of medical importance.

11:10 CCCM™: A Natural Product Approach to Cannabis-based Therapies

Andrea L. Small-Howard, Ph.D., Chief Science Officer and Director, GBS Global Biopharma, Inc. (Ottawa, Canada) and Chief Science Officer and Director, GB Sciences, Inc., (Las Vegas, Nevada)

GBS uses a novel, whole plant approach to discovering proprietary formulations of cannabis-derived compounds that show promise for the treatment of specific diseases. GBS has focused its efforts on finding therapies for patient groups that are largely underserved, and they are using novel delivery methods to ensure bioavailability and to provide time-released versions of their patent-pending, cannabinoid-containing complex mixtures (CCCM™).

Although many cannabis researchers and biophar-ma companies have focused on the activities of single cannabinoids, GBS leverages powerful molecular syn-ergies derived from whole plant extracts that are then further-refined and standardized. Most other canna-bis-based biopharmaceutical companies are studying one of the two most abundant cannabinoids in the plant, either tetrahydrocannabinol (THC) or cannabidiol (CBD); whereas, GBS embraces naturally occurring mixtures of approximately 480 bioactive compounds in the cannabis plant. GBS has demonstrated correlations between ex-tracts from different “chemovars”, chemical variations of the cannabis plant, and potential therapeutic efficacy for different specific human diseases.

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from the development and implementation of an FDA Good Manufacturing Practices (GMPs) quality system including the consistent manufacture of a higher quality cannabis product; more efficiency in overall operations with less waste; trained employees that follow procedures; prepara-tion in the event of a product recall; and most importantly ensuring the safety of products for your customers. Cus-tomers and investors alike, will be more attracted to your company because of your GMPs and the fact that you will be ready when the FDA assumes regulatory authority of the industry. All of this AND compliance with your state regula-tions. Be ahead of the curve, begin the practical implemen-tation of GMPs at your facility now.

Research Spotlight—Unlocking the Therapeutic Potential of Cannabis Derived Compounds

8:40 Hot Topics in Therapeutic Cannabis ResearchEthan Russo, M.D., Director of Research and Development, International Cannabis and Cannabinoids Institute, Prague

Cannabis has acquired a public reputation as a mira-cle drug that has not yet been supported by random-

ized clinical trials. However, it has proven extremely versatile in treatment in a wide variety of otherwise recalcitrant disorders through modulation of the endo-cannabinoid system (ECS). This presentation will focus on the scientific rationale from basic science research, available clinical data, and prospective formulation of cannabis-based medicines to treat brain tumors, Alz-heimer disease, traumatic brain injury (post-concussion syndrome and chronic traumatic encephalopathy), and endometriosis, all disorders where “conventional med-icine” has failed to produce acceptable results.

9:20 Cannabis-Based Drug Delivery: University Lab to Clinical Trials

Dr. Audra Stinchcomb, Professor, University of Maryland & Founder, F6 Pharma, Inc.

Topical, transdermal, and oromucosal dosage form development will be discussed. Primary research fo-cus areas will include microneedle-enhanced deliv-

ery and translational research models for public-private partnerships. Currently Dr. Stinchcomb is focusing sig-nificant effort in concert with the FDA on the evaluation of multiple dermal dosage forms in human subjects, with the end goal of creating validated in vitro-in vivo cor-relation studies that may help to improve the efficiency and cost of the drug development process. The research group is also developing the best way to formulate and evaluate drug delivery from oromucosal systems in vitro.

10:00 Morning Coffee & Networking Break


Canna-Pharma 2019

Our drug discovery process combines: 1) high throughput screening of tens of thousands of combinations of com-pounds derived from specific chemovars of the cannabis plant in well-established cellular models of diseases and 2) a proprietary network pharmacology algorithm for the prediction of complex therapeutic mixtures. By carefully screening the contributions of the individual compounds within our disease-specific chemovars, we discovered our patent-pending CCCM™ for the treatment of neurodegenerative disorders, inflammatory disorders, cardiovascular disorders, and chronic/neuropathic pain.

11:50 Lunch Break

1:00 Post-Lunch Presentation, Sponsored by

1:00 Compliance 101 for Cannabis CompaniesErin Northington, VP of Emerging Life Sciences & Clinical Solutions, & Diane Gleinser, VP of Life Sciences Services and Solutions, USDM Life Sciences

The ever-changing landscape of cloud technology and regulations have created opportunities for emerging life science companies to accelerate their journey to commercialization. The need to become and stay com-pliant while quickly ramping up an organization and rapidly implementing GxP technologies to facilitate

growth is critical to new life science companies. This presentation will focus on the top 3 things new cannabis life science organizations should plan for strategically to establish and maintain their GxP compliance.

1:20 Enhancing the Bioavailability of Cannabinoids in Pharmaceutical Dosage Forms

Jasmine Musakhanian, Scientific & Marketing Director, Gattefossé USA

With the looming ease of regulations around the globe, there is an expressed need for adequately dosed, age appropriate cannabinoid medicines. The window of

opportunities for new cannabinoid drugs currently in-cludes the treatment of multiple sclerosis, seizures, neu-ropathic/intractable pain in cancer patients, and nausea. There are also indications for anti-inflammatory effect, psychotherapy, and rehabilitation from opioid addiction.

Meanwhile, studies show that only 3-8% of orally admin-istered cannabinoids reach the systemic circulation. This poor bioavailability is in part attributed to the poor gas-trointestinal (GI) solubility of these compounds resulting in erratic and variable absorption from the GI tract. Ad-ditionally, cannabinoids undergo a significant first pass metabolism in the liver following GI absorption. These properties render cannabinoids as excellent candidates for Lipid-Based Drug Delivery (LBDD). This presentation discusses the key considerations for enhancing the de-livery of cannabinoids, focusing on LBDD for immediate or sustained action.

2:00 Complying with European Union (EU) Requirements for CBD and Medicinal Cannabis Producers to Gain EU Market Access

Marc Stegeman, Principal Consultant, ProPharma Group

In Europe, there is a growing market for medicinal cannabis as well as for CBD and more and more ma-terial will be required to satisfy the market. Suppose,

you are considering to enter this market. How would you approach that? What would be your strategy, what would be your products to sell and which requirements do you need to fulfill? My presentation will provide answers to these questions. It will include an overview of the le-gal status in the various EU-countries and discuss the EU-regulations on quality and regulatory aspects. More-over, it will discuss good distribution practice including im- and export licenses. Also, technical aspects of grow-ing, extracting and isolating of materials will be alluded to. Finally, an overview of clinical studies on Cannabis in Europe will be provided. In short: an update on the chal-lenges and opportunities regarding cannabis in Europe.

2:40 An Overview of the Therapeutic Potential of Cannabinoid Medicines Applied on the Skin

Theo Kapanadze, Ph.D., Co-Founder & Chief Scientific Officer, Diteba

Due to its wide variety of medical benefits, cannabi-noids are used to treat a number of common condi-tions, including chronic pain, inflammation, seizures,

insomnia, spasms, multiple sclerosis, and mental disor-ders such as anxiety and depression. As the topical prod-ucts, medical cannabinoids could be directly applied to certain areas of the body as an effective means of re-lieving pain and soreness, reducing inflammation, and soothing inflammatory skin conditions such as psoriasis, dermatitis, and eczema

For each pathology, it remains to be determined what type of cannabinoid and what route of administration are the most suitable to maximize the beneficial effects of each preparation and minimize the incidence of undesir-able reactions.

Due to low bioavailability of oral cannabinoids formula-tions, alternative routes of drug administration, including mucosal or sublingual dosing, vaporization of product and inhalation, and rectal administration, have been de-veloped to improve the amount of delivered cannabinoids.

The transcutaneous is another alternative route of can-nabinoid exposure that avoids first-pass metabolism and improves bioavailability. Also, transdermal delivery of cannabinoids is hoped to reduce negative side effects seen with inhalation or oral dosing products.

The main aim of our study was to evaluate In Vitro per-cutaneous absorption profiles of major (THC/CBD) alone, and in combination with minor cannabinoids onto and through human ex vivo skin dosing with varieties of ex-clusively developed topical formulations. Specifically,

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Canna-Pharma 2019

4:10 Cannabis Microbiome Sequencing: Implications for Cannabis Safety Testing

Kevin McKernan, CSO & Founder, Medicinal Genomics

The cannabis plant and cannabis products are highly varied and complex matrices. In the absence of rigor-ous study this immature industry has decided to adopt

methods commonly used in food testing to obtain infor-mation about the potential microbial hazards present. However, DNA sequencing of both the cannabis micro-biome and the conditions before and after culturing tell a tale of inaccurate methodology. Methods that are cur-rently being employed are leading the cannabis industry astray while blinding them to the real hazards that could be present. This presentation will walk you through the data that shows this and the discoveries we’ve made along the way that will hopefully open discussions for a fresh new perspective on how to tackle microbiological contaminants in cannabis.

4:40 Intellectual Property Munchies In Canna-PharmaParithosh Tungaturthi, Ph.D., J.D., Registered Patent Agent & Founder, LexKannabis, LLC

Medicinal cannabis has been gaining increasing pop-ularity over the last few years, in the United States as well as many countries around the world. Cannabis

garnered much attention for its potential in the treatment of chronic pain, Crohn’s disease, sickness related to can-cer medication, and many other conditions. The use and acceptance of cannabis therapy resulted in multiple new market entrants, including small biotech companies to large pharmaceutical enterprises. Significant financial investment is likely to be in the books for many compa-nies in producing and/or identifying a product that can be commercialized. A return on such investment can only be ensured by properly formulating and executing a—preferably global—strategy to protect the companies’ IP assets. Therefore, as the medical cannabis industry con-tinues its upward trajectory, it is not only important—but essential—for companies to effectively secure its IP in order to gain and maintain a competitive edge.

IP rights can prove to be vital components of success, es-pecially in an emerging market such as medical canna-bis. Given the complicated history of cannabis/marijuana legalization, there are many intricacies that the indus-try leaders must understand regarding securing rights around their technology. The potential problems that may occur when IP rights are ignored should not be over-looked, for the results can mean the difference between success and failure for a business. This presentation pro-vides an overview of IP strategies for protection of med-ical cannabis-related inventions, including protection of cannabis strains and related plants.

5:15 Close of Program

we aimed to compare and evaluate (24/48hrs) In Vitro ab-sorption profiles of the selected cannabinoids in enhance of In Vivo bioavailability. We also expected that the THC induced changes might be more pronounced after oral administration because of the expected presence of the potent psychoactive metabolite 11-OH-THC that could not be formed at all through the skin permeation. Finally, since THC and CBD are chemically related compounds, it has been reported that under certain (acidic) conditions, CBD can be cyclised to THC in vitro. More recently the important question has been raised as to whether CBD can also be converted to THC in vivo. Therefore our aim was to ascertain whether permeation CBD through the skin could result in the presence of THC and if so, this could potentially mediate therapeutic effects.

The collected samples analyzed on contents of canna-binoids by UPLC-MS/MS, In addition, the identification of minor cannabinoids and metabolites was achieved by means of UPLC-QToF. In vitro skin absorption, kinet-ic parameters obtained from both finite and infinite dose model have been calculated and assessed for character-ization of topical formulations

3:10 Afternoon Networking Break

Research Spotlight—New Analytical Approaches to Cannabis Safety & Testing

3:30 Tackling Pesticide Analysis in Cannabis: The Analytical Suitability of a Multi-Platform Approach

Dr. Anthony Macherone, Senior Scientist & Strategic Program Manager, Agilent & The Johns Hopkins University School of Medicine

Residual pesticide analyses in cannabis matrices iscomplicated because of matrix effects and target

analytes like pentachloronitrobenzene (PCNB) that are not amenable to common techniques using electrospray ionization (ESI). To overcome this issue, it has been sug-gested to use negative atmospheric pressure chemical ionizationliquid chromatography-tandem mass spec-trometry (Ni-APCI LC-MS/MS) for PCNB with a precursor ion of 275.5 m/z. However, a laboratorian must consider selectivity as much as sensitivity in the application of a certain analytical methodology and in this case, the ion-ization mechanism is reported as the loss of HCl followed by formation of an ammonium ion adduct. There are two intrinsic problems with this description 1) the empirical formula for PCNB is C6Cl5NO2thus there is no hydrogen atom to lose as H-Cl, and 2) the formation of a positive-ly charged ammonium ion in negative ionization mode is improbable. In this presentation we prove the correct ionization mechanism for PCNB using Ni-APCI LC-time-of-flight mass spectrometry (Ni-APCI LC-QTOF) and eval-uate the appropriateness of this analytical technique for PCNB in terms of selectivity, sensitivity, and the fit of the coefficient of determination compared to GC-MS/MS methodologies.

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Canna-Pharma 2019 Poster Presentations


below their maximum daily exposure as defined by the respective USP. The product was free of microbiological contamination.

Pharmacokinetic analysis of CBD plasma concentrations determined that the nano-lipid formulation had a Cmax of 72.0 ± 44.9 ng/mL with Tmax of 6.3 ± 2.1 hr, and the AUC was 557.8 ± 297.5 ng/mL*hr. Commercial comparators consisted of either full spectrum CBD or CBD isolate dis-solved in coconut oil or medium chain triglycerides. The maximum CBD concentration (Cmax) ranged from 28.1 to 64.5 ng/mL with a Tmax ranging from 5.8 to 8.0 hours. The AUCs ranged from 352.1 to 568.7 ng/mL*hr. Relative bio-availability of the commercial products was calculated to be between 63.1 and 102%.

The nano-lipid CBD formulation was nanosized, homoge-nous, and well characterized for cannabinoids, terpenes, residual solvents, pesticides, heavy metals, and micro-biological contamination. The pharmacokinetic profile of the CBD formulation showed earlier detectable levels of plasma CBD and reached peak plasma concentration 2 hours earlier than leading, oil-based commercial com-parators. The relative bioavailability of the CBD formula-tion was significantly greater than 2 of 3 oil-based CBD products. In conclusion, a water dispersible CBD product leads to faster absorption and greater exposure than oil-based products.

A Novel Microfluidic Approach for the Formulation of Cannabinoid Nanoparticles Natalia Sannikova, Tomas Skrinskas, Nathan Sykes and Kelly Sveinson, Ascension Sciences

Cannabinoids are susceptible to degradation in solution from light, temperature and au-

to-oxidation. They are highly lipophilic molecules with very low aqueous solubility (2–10 ug/mL) demonstrating low oral bioavailability and difficulty in entering the bloodstream. Nanoparticles for drug delivery offer solu-tions to these problems over traditional formulations such as efficient delivery of lipophilic drugs, protection from degradation and a tuneable therapeutic window in treating specific indications. Presented here is a method for formulating a wide variety of nanoparticles which has the potential to improve on incumbent techniques due to the speed and control afforded by the process.

The purpose of this study was to demonstrate the robust-ness and flexibility of microfluidic mixing in creating different types of particles (nanoemulsions, liposomes, polymer nanoparticles) and to showcase the tuning of particle characteristics (size, stability, encapsulation ef-ficiency). Microfluidic mixing has been used extensively in formulating nucleic acid lipid nanoparticles where a low energy, bottom up approach that enables self-assem-bly of the particles is advantageous for rapidly tuning characteristics and repeatability. Applied to cannabinoid nanoparticles, the method allows the synthesis of drug loaded nanoemulsions, polymer nanoparticles and a wide variety of lipid-based systems.

Characterization and Pharmacokinetics of a Novel Nano-Liposomal Delivery System of CannabidiolMike Sandoval, Santé Laboratories

Cannabidiol (CBD) is a prominent phytocannabi-noid constituent of Cannabis sativa (Cannabis) that lacks the psychoactive effects of D9-tetra-

hydrocannabinol (THC). CBD has been reported to have broad therapeutic properties across a range of disorders including anxiety, depression, inflammation, pain, and seizure disorders either when administered alone or with THC. Evidence of CBD’s therapeutic properties is largely limited to preclinical studies (11). However, in June 2018 the FDA granted approval of Epidiolex, a CBD isolated from marijuana for the treatment of pediatric seizure dis-orders, demonstrating the efficacy of CBD in a controlled clinical trial setting.

As the CBD market flourishes, manufacturers of such con-sumer products will experience an increase in regulation and oversight at the state and federal level, including the accuracy of the product’s reported CBD concentration. In 2017 survey, 69% of consumer CBD products (n = 84) in the categories of oils, tinctures, and vaporizing liquids were found to be reported inaccurately (more than ± 10% than label claim), underscoring the need of regulatory agen-cies to take steps to ensure CBD products are sufficiently characterized and tested.

The nano-lipid formulation described herein brings in-novation to the CBD landscape leveraging a thorough and diligent approach to consumer product developed with pharmaceutical drug development standards. The nano-lipid delivery system imparts apparent aqueous solubility to an otherwise practically insoluble mole-cule. Critical quality attributes of the final product were measured to generate a certificate of analysis. Physical and chemical stability of Reset Balance was determined under several storage conditions. Lastly, the oral phar-macokinetics of Reset Balance were measured in a mini-pig model and compared to two oil-based commercially available products.

The nano-lipid CBD formulation was white in appear-ance, not transparent, free of visible particulates and did not sediment. The average particle size was 116.9 nm and had a polydispersity index of 0.061, indicating the pop-ulation distribution was nano-sized and highly homog-enous. The zeta potential was slightly above neutral at +6.26 mV and consistent with the ingredients having a net neutral charge.

The nano-lipid formulation was manufactured at a CBD concentration of 20 mg/mL and HPLC analysis of the final product was found to be within 10% of the target con-centration. CBD was the only cannabinoid detectable in the product. Residual solvents were quantified accord-ing to USP <457>, and none were detectable in the prod-uct. Heavy metals (USP <232, 233>) and pesticides (USP <561>) were also found to not be present or significantly


Canna-Pharma 2019 Poster Presentations


understanding, along with effective controls based on science and quality risk management. Key QbD elements include identification and documentation of control strategies for both the process and product, such as a Target Product Profile (TPP), Critical Quality Attributes (CQAs), Critical Material Attributes (CMAs), Critical Process Parameters (CPPs), to ensure process capabil-ity and continuous improvement. Here, we present case studies on the successful application of QbD approaches to cannabis process, formulation and analytics, towards the development of standardized medicinal products for oral administration.

The US Vaping Crisis: Legal and Illicit Cannabis Cartridge AnalysesAaron Riley, President, CannaSafe

In response to recent vaping related ill-nesses, CannaSafe took a deeper dive into

this issue by expanding its initial findings and provid-ing further insights into the current state of regulated cannabis. CannaSafe performed its own testing on vape products purchased from the legal, regulated market and compared the results against products purchased, from the illicit market. The 104 legal, regulated vape products tested met the label claims of THC concentrate percent-ages, contained no Vitamin E Acetate, and did not fail for pesticides. Out of 12 illicit vape products tested, nine contained up to 38.5% of Vitamin E Acetate, and all of them had detectable levels of pesticides, including my-clobutanil, which can break down into hydrogen cyanide when heated. Seven of the illicit vape products had THC percentages that were significantly inconsistent with what was labeled on the packaging.

All the illicit products CannaSafe tested would have failed California Phase III compliance testing, meaning that none of the products from the illicit supply chain would have made it through California regulatory stan-dards and onto the shelves of licensed retailers. These results prove it is more difficult for these types of adul-terants to enter a regulated market. Vitamin E Acetate was the first dangerous additive in the illicit market to make headlines, but it certainly will not be the last. The cannabis industry has come together to propose solu-tions to combat counterfeit products and identify ap-proved sources for additives. We conclude that a ban on vaping would only endanger the progress made and force vulnerable patients back into unsafe and unregulated markets where dangerous products thrive. On behalf of the cannabis industry, CannaSafe urges lawmakers not to take this delivery method away from patients and consumers.

Particle sizes were tuned for each formulation and ranged between 40 to 100 nm with polydispersity aver-aging 0.13. Formulations demonstrated size and concen-tration dependent (oil to excipient concentration ratio) encapsulation efficiency and stability over time.

Our results demonstrate the flexibility, repeatability and tunability of microfluidic mixing in producing a wide range of nanoparticles.

CBD for Beauty and Skin DisordersDr. Jeanette Jacknin, MD, Dermatologist, Consultant/Author, Smart Medicine for Your Skin (2007)

This poster presentation will give a brief overview of what the endocannabinoid system is, and how it is

involved in the skin. It will summarize very recent scien-tific studies behind cannabinoids and anti-aging, acne, itch, eczema, and psoriasis. It will also include a summa-ry of what products are already on the market, and where that market is projected to extent to.

Key Chemistry, Manufacturing, Controls Considerations for the Development of Medicinal Cannabis Products for Oral AdministrationTuna Yucel, Ph.D., Greg Fahs, Wenmin Yuan, Ph.D., Nick Boylan, Ph.D., Oren Levy, Ph.D., Parallel

Parallel is a leading, global company that is pioneering human well-being, and improving the quality of lives of humanity through the

benefits of cannabinoids. We follow rigorous operations and business practices to ensure the quality, safety, con-sistency and efficacy of our products through advancing cannabis science, research and development.

A 2017 report by the National Academies of Sciences, Engineering, and Medicine highlights the need for stan-dardization in cannabis research methodology due to (1) wide variety of different cannabis strains; (2) variation in the concentration of active substances in cannabis; (3) lack of a standardized dose; and (4) existence of diverse routes of administration. Our goal is to be at the fore-front of cannabis research and development, addressing challenges facing the cannabis industry, including those highlighted in the National Academies’ report.

To that end, we routinely apply systematic pharmaceu-tical Quality by Design (QbD) approaches to cannabis product development. QbD begins with predefined ob-jectives, emphasizing thorough product and process

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