GMP#19 – Pharmaceutical Oral Cannabis Drops Product Development Authored By: Michael Sassano & Antonio Guedelha      In the pharmaceutical industry, all products must be approved by the local authorities of the countries where manufacturers will sell them. For pharmaceutical cannabis products, different countries in the European Union have disparate requirements. For example, Germany only allows magistrally prepared oral cannabinoid drops, while Portugal enables companies to register finished-form oral drops. Understanding the laws in your target countries is imperative for your company’s success.

Documentation Required for Oral Cannabinoid Product Development

Several requirements must be observed when developing a narcotic medicine in Europe.  Quality and stability studies are the basis of all herbal medicines, including cannabis. The use of excipients approved for pharmaceutical product manufacturing is also necessitous. Finally, some countries may require only parts of the dossier of registration for Marketing Authorization (MA), while others may require clinical studies.

The MA Dossier and Pharmaceutical Oral Cannabis Products

The MA dossier content is guided by many regulations, including legislation (EU directives and regulations), European Commission notice to applicants (2B), presentation and content of the dossier, pharmacopoeias, guidelines (ICH or regional-specific), and more. Part 3 of the dossier content must include a significant amount of information, much of which comes from the suppliers. Required information includes the product’s commercial name, product information, drug substance, manufacture, characterization, control of drug substance, reference standards or materials, container closure system, and stability. 

The Manufacturing Process of Cannabis Oral Drops

For cannabis oral drops, you must define your products and develop the formula and manufacturing process. 

Manufacturing Pharmaceutical Cannabis Extracts for Oral Drops

The manufacturing process begins with dry cannabis flowers. Manufacturers extract and distill CBD or THC extract from plant matter.  Regardless of your chosen extraction method, verifying that all equipment and materials are pharmaceutical-grade is essential. Take care when choosing your supplier, as not all extraction equipment is easy to validate in the pharmaceutical industry. Requesting proof that a machine is used already in an EU-GMP pharmaceutical manufacturing facility is a simple way to verify that a supplier’s equipment is pharmaceutical-grade. References are critical, and suppliers should provide them.

Cannabinoid Oral Drop Excipients, Reactors, and Formulations

After manufacturing cannabinoid extracts, these base APIs can be used for formulation inside a reactor with your excipients.  There are many sizes of reactors, so be aware that you must validate your process by filling up the reactor. If the reactor is too large, you will spend too much money making validation batches, which you cannot sell. It is essential to gauge your market correctly and determine the best size. Excipient selection is also critical. If you don’t select the proper excipients from an appropriate source of pharmaceutical quality, your products will be unsellable. There are many choices for excipients used to make oral drops. Some are better-tasting, while the body may more readily absorb others. Stability is also vital, so ensure your choices provide the best results. Oral drops typically combine THC, CBD, and carrier oil. Remember to check the source and purity of the extract and the carrier oil you select, as some countries have limitations.

Primary Cannabis Oral Drop Packaging

Oral drops come in several sizes, so choose the best option for the market you are entering. 25-millilitre and 30-millilitre bottles are the most common, but many other sizes are also available.  You also need to pay attention to your cap. Some markets require magistral-format screw caps, others require child-resistant screw caps with syringes, and some allow droppers. All parts of the primary packaging must be approved for pharmaceutical use, including the bottle color, material, cap type, dosage mechanism, and even the label.

Secondary EU-GMP Cannabis Oral Drop Packaging

All texts in the secondary packaging must comply with GMP rules and legal requirements. The batch number and expiry date must be present. Depending on the country, many other data points may need to be provided on the label or printed on the secondary pack, such as the manufacture date, box serial number, etc.

Development of the Oral Cannabis Drops Product

When developing cannabis oral drops, you must consider all factors.  Remember to: define the product; define the concentration; pack; produce three batches; analyze; make stability studies; collect all data in MA dossier part 3; submit to the relevant authority; and attain approval. It’s easier said than done.  You should use a product development sheet to support the management. This document should have all information about the development project and be one A4 page at maximum. A Gantt chart to manage the development process is often helpful as well. With these targets, you can develop and sell pharmaceutical cannabis oral drops.