FDA's History with Complex Plants

Pharmaceutical Executive spoke with Ajna Biosciences founder and CEO Joel Stanley about the current regulatory landscape surrounding cannabis, hemp, and other medications from botanicals. As he discusses, this is an area where only a few medications have made it through FDA’s approval process, which has different complications from botanically derived or synthetic compounds.

Pharmaceutical Executive: Can you discuss FDA’s history with complex plants?
Joel Stanley: In 2004, FDA released its first botanical drug guidance to the industry. This was the first time that complex botanical drugs would be allowed through FDA’s process for pharmaceutical approval.

That guidance was updated in 2016, which is the current guidance that the industry relies upon. Since 2004, only four botanical drugs have been approved.

Many people don’t understand between botanically derived drugs, which are single molecule compounds. These can be synthesized or derived from nature. About 20-25% of single compound drugs are botanically derived.

A botanical drug is a complex mixture (a crude extract from a plant or fungus) and can sometimes have hundreds or even thousands of compounds that must be standardized. It’s a very complex regulatory landscaped on the front end, where your chemistry, manufacturing, controls, and drug characterization is a very different process. It’s hard to standardize.

That’s part of the reason why we only have four FDA-approved botanical drugs.

PE: How are you advancing full-spectrum cannabis through FDA’s pathway?
Stanley: Our first drug in the pipeline recently received clearance for its Phase 2 trial. This is AJA001 and is done under a joint venture between Ajna Biosciences, my old company Charlotte’s Web, and British American Tobacco.

This is for autism spectrum disorder. We had a long headstart standardizing a cannabis plant (hemp) with high CBD and low THC. We spent about two decades working on standardizing and replicating the hemp plant.

What we have to in the lab is characterize the molecules. When you think any botanical drug, there’s a lot of work on the front end. You must know your specific plant genetics, which growing region, and is it going to produce the same ratio of vital molecules every time.

Now we take that standardized process to the laboratory and characterize all the molecules. The first drug, coming from hemp, has over 6,000 compounds identified. That shows the complexity of nature.

We’re at the point where we can propose a Phase 2 trial.

PE: What issues impact access for patients on plant-based therapies?
Stanley: When it comes to hemp with high THC and hemp with high CBD, these are two different regulatory environments. Recently, language was added to the farm bill that redefined hemp.

In my opinion, it was catastrophic language, although I believe it will be fixed.

In essence, if it stays as is, it would ban the majority of high CBD hemp products on the market. This is massive because there are millions of families out there using these products and claiming to use them to great effect.

A lot of people ask how this will affect our drug development pathway. The truth is that it really doesn’t. We have DEA licensing and we’re FDA registered.

We’re not operating in the dietary supplement space or retail marijuana state-to-state programs. These legislation quirks for cannabis products don’t really affect us, but they make what we’re doing that much more important. If these products aren’t available for people, at least we’re moving something through that will be available in all 50 states and be covered by insurance.