Marijuana Business Magazine April 2020

Marijuana Business Magazine | April 2020 80 supposed to start in January and last eight weeks. In addition to getting FDA approval for the study, CT Pharma needed a research license from the Connecticut Department of Consumer Protection, which conducts regular visits at CT Pharma. “There were many moving pieces to bring this together,” Ferrarese said. CT Pharma’s success attracted investments from private equity groups Tuatara Capital and Bonaverde Capital, which acquired the cannabis outfit about 18 months ago. “They were attracted by the research aspect of the company and the potential of a new drug application,” Ferrarese said. Ferrarese believes the end result will be an FDA-approved tablet that will be on the market within five years. The estimate is based on the time between when the FDA first approved GW Pharmaceuticals’ Epidiolex product for study (2013) and when the agency approved Epidiolex for market (2018). TETRA BIO-PHARMA’S SMOKE STUDY Tetra Bio-Pharma CEO Guy Chamberland had worked with FDA regulators since 1995, but despite his professional experience, “the FDA wasn’t too happy” when he first broached the idea of bringing to market a smoked cannabis drug to treat pain in end-of-life cancer patients in June 2016. But after several meetings with FDA officials and a rule change that gave him an opening, Chamberland succeeded. How did he do it? In November 2016, the FDA revised guidelines about drug-delivery devices that Chamberland believed would allow him to characterize pipes and vaporizers as delivery devices, with cannabis smoke and vapor (as opposed to dried flower) serving as the drug. In a meeting with the FDA shortly after the device regulations were revised, “we laid out how we would develop and bring to market a prescription drug that was going to be smoked with a pipe and dried bud,” Chamberland said. “We laid down our full plan for the Phase 1 trial and the trials that would be Phase 2 and 3, and then all the way to the market. We made some proposals to them on the toxicology requirements as well as further regulations (and) how we saw the device being approved,” he said, adding that the FDA provided Tetra Bio-Pharma with more than 29 pages of detailed guidance. “The FDA laid down what they expected not to see in the smoke. And they were the ones that pushed us to go out there and really quantify everything that was entering the patients’ lungs and really have a look at it. So we did achieve that, and they wanted us to relate that back to the fresh plant, which we did.” In the Phase 1 trials, conducted in Canada, volunteers smoked and vaped three varieties of cannabis provided by Ontario-based Aphria while researchers measured what was in the smoke and vapor—and whether it was safe. Chamberland and other Canadian researchers set up their studies to comply with FDA guidelines so they can show that previous studies have been done according to the agency’s standards. “We amassed a massive amount of clinical data in volunteers and in the lab, and it gave us a very clear insight into how cannabis works in patients. And that’s accelerated our program to where we are today,” Chamberland said. Some of the most pivotal data had to do with smoke and vapor composition, dosing and mycotoxins. “In that research, we ended up discovering some very unique aspects to smoke versus vapor. We described from a regulatory point of view that vaped cannabis is different Steps for Cannabis Drug Studies Step 1: Sponsor obtains number to request a pre-Investigational New Drug (IND) meeting. A pre-IND meeting is an optional opportunity to obtain U.S. Food and Drug Administration guidance on sponsor research plans and required content for an IND submission. Step 2: Imported controlled substances are subject to U.S. Drug Enforcement Administration authorization. The sponsor contacts the National Institute on Drug Abuse or another DEA-registered source of cannabis to obtain information about the specific cultivars available, then includes all necessary information in the IND application. Step 3: The sponsor might contact the DEA to discuss Schedule 1 drug research plans that might require DEA inspection for an investigator and study site licensure. Step 4:  If the selected raw material or drug substance manufacturer holds a Drug Master File, the sponsor must obtain a Letter of Authorization. Alternatively, an IND submission would need to contain all data characterizing the study drug and ensuring it is safe for use in humans. Step 5: The sponsor sends a copy of the IND application and clinical protocol, including a Letter of Authorization, to the FDA. Step 6: The FDA reviews the IND application. The sponsor must wait 30 calendar days after an IND submission before initiating any clinical trials, unless the FDA notifies the sponsor that the trials might proceed sooner. During this time, the FDA has an opportunity to review the submission for safety to ensure that research subjects will not be subjected to unreasonable risk. Step 7: If the IND is authorized by the FDA as “safe to proceed,” the sponsor may submit their clinical protocol registration application to the DEA to obtain protocol registration. Once this is received, the sponsor obtains cannabis and/or cannabis-derived substances from the National Institute on Drug Abuse or another DEA- registered source to begin the study. Source: U.S. Food and Drug Administration Guy Chamberland Courtesy Photo Research Project