Development of cGMP Manufacturing Process for CBD

DESCRIPTION provided by applicant Medical marijuana is now approved in states and the District of Columbia for several medical conditions such as cachexia cancer chronic pain epilepsy and other disorders characterized by seizures glaucoma HIV AIDS Multiple Sclerosis muscle spasticity and nausea Progress has been made on several fronts on the use of cannabinoids for medical use such as Charlotteandapos s Web CW being used for childhood epilepsy through ad hoc development by patient advocacy groups Sativex GW Pharmaceuticals England a drug containing equal proportions of THC and CBD was recently approved as a second line treatment for Multiple Sclerosis MS associated spasticity in Canada New Zealand and European countries The ready availability of pharmaceutical grade CBD and a standardized CW product manufactured following cGMP guidelines will facilitate clinical evaluation by NIH investigators and other researchers for epilepsy MS and other CNS diseases The developed process will also be utilized for the manufacturing of THC already in use for cancer pain and nausea and AIDS related cachexia and other cannabinoids in development The primary goal of this research program is to develop a process for manufacturing pharmaceutical grade CBD following current Good Manufacturing Practices cGMP of the US FDA for use in clinical trials for childhood epilepsy and other CNS indications by the NIH and other researchers Our secondary goal is to develop a standardized enriched CBD fraction similar to Charlotteandapos s Web CW for use in childhood epilepsy We hypothesize that CBD and CW can be cost effectively manufactured from high CBD content Cannabis sativa hemp utilizing supercritical fluid technology and that such a process could also produce other bioactive cannabinoid mixtures for future research and therapeutic use We propose to manufacture pharmaceutical grade CBD andgt and andlt THC and a standardized CW fraction CBD and andlt THC both following cGMP guidelines by utilizing supercritical fluids and near critical fluids with or without polar co solvents such as alcohols SuperFluids These fluids are gases such as carbon dioxide which when compressed exhibit enhanced thermodynamic properties that can be andquot fine tunedandquot for rapid and selective extraction of bioactive molecules We will obtain sufficient quantities of high CBD content Cannabis sativa from growers in Colorado Maine or Massachusetts and or NIDA to conduct the proposed research Under the newly passed Farm bill recently signed by President Obama the farming and intra state transportation of hemp andlt THC are now exempt from the Schedule requirements of the Drug Enforcement Agency Since Aphios has been an approved Schedule research facility with DEA license No RC to research and develop DEA Schedule products Our license is renewed annually Our Phase I Specific Aims are as follows Establish optimum conditions for the selective SuperFluids fractionation of Cannabis sativa to Isolate CBD with absolute purities andgt and andlt THC Define SuperFluids chromatographic purification conditions for the further purification of CBD with absolute purities andgt and andlt THC and Establish downstream chromatographic conditions for the final purification of CBD with absolute purities of CBD andgt and andlt THC Our Phase II Specific Aims are as follows Design cGMP processes for SuperFluids CXP and segmentation chromatography of Cannabis sativa to produce standardized CW and pharmaceutical grade CBD Modify extant SuperFluids CXP Unit construct segmentation chromatography systems and upgrade facility to manufacture standardized CW and pharmaceutical grade CBD following cGMP Manufacture a minimum of back to back large scale batches of CW and CBD following cGMP guidelines and document in batch records and product release and Document manufacturing process in a CMC chemistry manufacturing and controls for IND applications to the FDA and establish a Drug Master File DMF with the FDA In Phase III we will manufacture pharmaceutical grade CBD for clinical evaluation by the NIH and other pharmaceutical companies and standardized CW for use by medical marijuana dispensaries in Massachusetts and other states In order to avoid intra state trafficking issues with the Federal government we will sell small scale CXP manufacturing units process conditions and supporting documentation for manufacturing standardized CW products to other state with medical marijuana dispensing laws The legitimate use of marijuana for several medical indications has far outpaced the medical and clinical evaluation of marijuana and specific cannabinoids for different medical uses In the National Institutes of Health convened an Ad Hoc Expert Panel to discuss current knowledge of the medical uses of Cannabis The report discussed the importance of other cannabinoids and their potential interaction effects upon THC stating andquot Varying proportions of other cannabinoids mainly cannabidiol CBD and cannabinol CBN are also present in Cannabis sometimes in quantities that might modify the pharmacology of THC or cause effects of their own CBD is not psychoactive but has significant anticonvulsant sedative and other pharmacological activity likely to interact with THC andquot The Institute of Medicine IOM concluded that scientific data indicate the potential therapeutic value of cannabinoid drugs primarily THC for pain relief control of nausea and vomiting and appetite stimulation and clinical trials of cannabinoid drugs for symptom management should be conducted We propose to manufacture pharmaceutical grade CBD for clinical evaluation by the NIH and other pharmaceutical companies for Multiple Sclerosis and other CNS diseases and a standardized Charlotteandapos s Web CW product for use by medical marijuana dispensaries in Massachusetts and other states for childhood epilepsy PUBLIC HEALTH RELEVANCE The legitimate use of marijuana for several medical indications has far outpaced the medical and clinical evaluation of marijuana and specific cannabinoids for different medical uses In the National Institutes of Health convened an Ad Hoc Expert Panel to discuss current knowledge of the medical uses of Cannabis The report discussed the importance of other cannabinoids and their potential interaction effects upon THC stating andquot Varying proportions of other cannabinoids mainly cannabidiol CBD and cannabinol CBN are also present in Cannabis sometimes in quantities that might modify the pharmacology of THC or cause effects of their own CBD is not psychoactive but has significant anticonvulsant sedative and other pharmacological activity likely to interact with THC andquot The Institute of Medicine IOM concluded that scientific data indicate the potential therapeutic value of cannabinoid drugs primarily THC for pain relief control of nausea and vomiting and appetite stimulation and clinical trials of cannabinoid drugs for symptom management should be conducted We propose to manufacture pharmaceutical grade CBD for clinical evaluation by the NIH and other pharmaceutical companies for Multiple Sclerosis and other CNS diseases and a standardized Charlotteandapos s Web CW product for use by medical marijuana dispensaries in Massachusetts and other states for childhood epilepsy