The analytical methods were developed and validated and in particular the method to test the release of API from the chewing gum. A chewing gum tester as per European Pharmacopoeia was used to demonstrate that release from such a complex matrix is possible and this method was also validated according to ICH-guidelines.
Whether extracts or purified cannabinoids are used during these studies, there are several possibilities to administer active substances to patients; each with their own pros and cons.
When working with medicinal cannabis, it is important to start with the patient in mind and define requirements that will treat a patient in the most comfortable / appropriate way possible.
During development of the chewing gum, it soon became apparent that this was by no means an easy task. Both CBD and THC have a strongly lipophilic character and on top of that are unstable under oxygen and light conditions (except when CBD is in its crystalline form). It is well established that THC decomposes by a radical oxidative process. This precludes the simple mixing of ingredients to form a chewing gum as would typically be done in a tableting process. The lipophilic character of both the chewing gum and the APIs form a combination that will not easily separate and dissolve into the hydrophilic environment of saliva. On top of that, the unprotected APIs would not survive in such an oxygen-rich environment.
After deciding on the TPP, a dedicated project team was set up to address all the activities needed to progress to the first clinical study which would be a PK/PD-study with the chewing gum containing THC. ProPharma Group has a network of over 1,100 in-house and external subject matter experts on formulation and analytical as well as on quality and regulatory aspects and clinical.
The clinical study will be conducted by a clinical CRO. The CRO developed the clinical protocol and supporting plans and related documents around data management, safety reporting, lab assessments, monitoring, etc. The sponsor/client maintains overall responsibility for the conduct of the study. Competent authorities advised that GCP compliance should be supported by an external person to ensure no bias towards the results and possible issues during the study. ProPharma Group GCP expert will support this aspect of the project.
The medicinal cannabis industry is rapidly maturing.
Each work stream was led by a project lead who represented his or her specialty within the core project team. The team was completed with a sponsor representative and a Project Manager. The core team was mainly focused on overall planning and resolving of issues, rather than on the technical aspects of the project. Technical aspects were dealt within the sub-teams and issues were escalated if these could impact the timelines, budget or compromise the desired outcome of the project. The team structure is depicted in the scheme below.
There are quite a few patient groups strongly advocating the use of THC, CBD or mixtures for treatment of various conditions such as PTSS, ADHD and pain. They often report that they have found in cannabinoids an effective treatment for their ailment after a long search for the best combination of active substance, administration route and delivery device. Can we consider cannabinoids as possible personalised medicines in which for every patient a unique combination is needed? To continue the studies to discover more about treatment with cannabinoids, it is important to be able to navigate the field with an expert to support the processes.
The oral route is known to deliver only low amounts of THC due to a first pass effect i.e. clearance of THC by the liver, which results in a bioavailability through the oral route of only 15%. It was speculated that mastication (chewing) would also have a positive effect on pain one of the possible indications. The use of other modes of oromucosal delivery were excluded as those would not require mastications. On this basis, ProPharma Group was asked to develop an overall development plan including formulation, regulatory and clinical strategies.
ProPharma Group talk us through the process of creating a trial using chewing gum containing THC.