Powering the potential for innovation in this space, there is an increasing need to accelerate patient access to possibly life-changing cannabinoid-based treatments.
However, entering an emerging and advancing industry — such as the cannabinoid market — can be intimidating.
Indeed, because the scientific understanding of these ingredients is still relatively novel, only a few companies have effectively steered cannabinoid-based pharmaceuticals through the drug development and approvals process.
Nonetheless, as the understanding of these unique molecules and their promising therapeutic benefits grows, players throughout the industry are becoming more adept at navigating this evolving terrain.
As a trusted end-to-end partner in the cannabinoid arena, dsm-firmenich — together with Brains Bioceutical — is enabling drug developers to unlock new possibilities in cannabinoid research and development … and inspire next-generation patient-centric treatments.
In this article, Athanasia Kanli, Global Market Development Manager, Pharma, at dsm-firmenich, discusses some key considerations within the drug development pathway to minimise the risk of setbacks and enhance the chances of achieving significant therapeutic breakthroughs in this field.
Why and how to choose the most appropriate API for your drug development
Selecting the right active pharmaceutical ingredient (API) underpins the success of any drug development project from the beginning.
This is particularly important in the cannabinoid arena, wherein emerging ingredients are surrounded by misconceptions and the regulatory framework governing them is rapidly developing.
Kanli urges drug manufacturers from the very start of their product development process to stop and ask: is my cannabinoid API registration-ready?
This is the best approach to effectively mitigate the risk of failure during cannabinoid research and development, increase the odds of therapeutic advancements and build robust scientific evidence — and also save valuable time and resources along the way. Here are three key considerations when selecting the most suitable API for the task.
GMP certification
Good manufacturing practice (GMP) certification might not seem like an essential consideration at the preliminary stages of the cannabinoid drug development process; non-GMP pharma-grade ingredients may sometimes be used for early stage clinical trials in some regions.
However, it is wise to choose a GMP-certified API right from the very beginning of the journey. Why? Because when a drug reaches Phase II human trials and on every subsequent step towards market authorisation, it is compulsory to have an API developed under GMP quality conditions and in a facility audited and certified by a national competent authority.
Switching from a non-GMP to a GMP API while already engaged in the drug development process can incur risks and costs to pharmaceutical product development, including the major risk of having to redo trials because of differences between the APIs used (such as impurity profile or bioavailability).
Our advice: play it safe and always choose a GMP-certified API from the start.
Regulatory documentation
Regulatory documentation, including robust data packages and proof of quality, is mandatory for clinical trials and drug product registration. Ideally, the API should be supported by the relevant documents, such as a Drug Master File (DMF)/Active Substance Master File (ASMF) for launch in the US and Europe.
In addition, choosing a supplier that provides robust safety and stability data is essential when selecting a cannabinoid API for drug development.
Cannabinoid ingredients that are high in purity are also necessary to ensure that external factors don’t interfere with the safety and efficacy of the final drug product.
To guarantee a cannabinoid API is the highest purity, it should meet stringent quality and purity standards defined by the European Pharmacopoeia (Ph. Eur.), the United States Pharmacopeia (USP) and any applicable quality guidelines set by the International Council for Harmonization (ICH).
Natural versus synthetic
Cannabinoids can be either natural (derived from the Cannabis sativa plant) or synthetic (chemically developed in the lab). Why does this matter? As an example, synthetic cannabidiol (CBD) APIs can exhibit specific impurities, including a risk of enantiomeric contamination of the drug substance.
This could lead to greater safety and toxicity concerns.1 Plant-based actives have a natural structure and stereochemistry that influences receptor binding and the biological function of the molecule.
Kanli points out that synthetic CBD has also been prohibited by several regulatory authorities around the world, highlighting another reason to opt for a natural cannabinoid API.
Furthermore, the proposed Ph. Eur. monograph for CBD, compliance with which is mandatory for pharmaceutical products to be developed and registered in Europe, requires that the CBD API is derived from natural sources.
Moreover, naturally derived cannabinoids are more popular than synthetics with patients. For instance, 75% of patients with epilepsy prefer natural CBD compared with synthetic alternatives.2
In summary, drug manufacturers should ensure that their API for cannabinoid drug development is manufactured in a GMP-certified facility, of high purity, supported by good regulatory documentation and, in the case of CBD, of natural origin. This is key to gaining a competitive edge in the market and long-term success.
The art of crafting patient-centric drug products
Patient-centricity in drug product design is a fundamental approach that leads to more effective, safer and better-tolerated medications.
By putting the patient at the centre of the drug development process, pharmaceutical companies can achieve better treatment outcomes, improved patient satisfaction and a stronger position in the market.
The cannabinoid arena is dominated by liquid applications, which patients often need to consume in large volumes to achieve a positive therapeutic outcome. Not only is this an unpleasant experience but also introduces potential complications, leaving the market in need of a solution that puts the patient first.
When it comes to patient-centricity in the pharmaceutical space, one format comes out on top: solid oral dosage forms. Patients and formulators prefer this format as it offers several advantages, including good compliance and ease of ingestion.
However, crafting solid oral dosage formats with cannabinoid APIs comes with its own unique set of challenges owing to the physiochemical properties of cannabinoid molecules.
A lens on bioavailability
The highly lipophilic nature of cannabinoids diminishes the molecule’s bioavailability after oral administration, which can be as low as 6%.3
This creates a unique opportunity to optimise the bioavailability of cannabinoids, which will reduce the volume of the drug required to achieve a therapeutic benefit.
This will open up a new level of patient-centricity in this space, thereby reducing dosage requirements and minimising the likelihood of side-effects.
What’s more, enhancing bioavailability may enable the development of more therapies that are compliant with regulatory access pathways (which currently restrict the maximum daily dose of API that can be administered to a patient).
Beyond bioavailability, stability, solubility and drug loading are also key factors that influence the success of oral solid dosage formulations. dsm-firmenich is exploring new, cutting-edge technologies to support high drug-loading, good physical/chemical stability and optimal oral bioavailability in cannabinoid formulations.
Enter the market with confidence
Success in cannabinoid drug discovery and development requires a 360° view of the complex, lengthy and demanding development pathway.
It also relies on access to deep expertise and leading-edge capabilities at each stage of the drug development journey — from target identification and initial research to market launch.
dsm-firmenich, together with Brains Bioceutical, offers a unique end-to-end innovation platform designed to unlock customised cannabinoid-based therapeutics, with a spotlight on exploring the science behind cannabinoids in promising indications such as pain management, stress and anxiety.
The offering includes a robust cannabinoid API portfolio that is of the highest and purest quality, GMP-certified, registration-ready and available in finished dosage form.
We also bring leading-edge technical expertise and the regulatory know-how that drug developers need to navigate the ever-changing cannabinoid market with confidence.
References
- D. Cushing and B. Joseph, “Synthetic Cannabinoids Severely Elevate Amino Transferase Levels. Natural Cannabidiol Does Not,” Journal of Medical Phyto Research 2, 1-13 (2018).
- R. von Wrede, et al., “Plant Derived Versus Synthetic Cannabidiol: Wishes and Commitment of Epilepsy Patients,” Seizure: European Journal of Epilepsy 80, 92–95 (2020).
- E. Perucca and M. Bialer, “Critical Aspects Affecting Cannabidiol Oral Bioavailability and Metabolic Elimination, and Related Clinical Implications,” Cannabinoids in Neurology and Psychiatry 34(8), 795–800 (2020).