Botanical Drug Market Hampered by Regulations

WELLESLEY, Mass.The global botanical drug market will grow from $21.4 billion in 2011 to $22.1 billion in 2012, reaching $26.6 billion in 2017, according to a new report from BCC Research. The five-year compound annual growth rate (CAGR) will be 3.7 percent, the market research firm expects, which is lower than expected just a few years ago.

BCC Research breaks the botanical drug market into two segments, botanical drugs, which are expected to have a value of $10 million in 2012 and $599 million in 2017 (CAGR of 126.7 percent), and all other plant-derived drugs, which should total $22.1 billion in 2012 and $26.6 billion in 2017 (CAGR of 3.7 percent).

Plant-derived drugs, as termed in the report, are single molecular entities, and botanical drugs are mixtures (polymolecular) of vegetable materials that may include plant materials, algae and macroscopic fungi. Botanical drugs may lack a distinct active ingredient, with the drugs activity possibly coming from multiple active compounds.

BCC Research said this report predicts a smaller growth for botanicals than it previously expected due to the slowing economy and increased regulatory hurdles. FDA finalized its guidance on botanical drugs in 2004 to help companies that want to market botanicals as OTC drugs or prescription drugs get FDA approval, but pharmaceutical companies are still confused by the regulations, BCC said, and they likely will be through 2017.

Mark Blumenthal, founder and executive director, the American Botanical Council (ABC), explained, in 2004, FDA removed some of the preclinical toxicology requirements that are normally associated with drugs to create a category of botanical drugs. Botanicals, as natural materials that have been part of the human food supply, are seen as less risky than conventional pharmaceutical drugs that are usually synthetic novel chemicals that have not been exposed to humans.

Michael McGuffin, president, American Herbal Products Association (AHPA), said about 500 have been submitted in total. McGuffin noted FDA gets about four or five botanical drugs submissions each month.

However, only one has made it through as an approved drug: Veregen®, a green tea extract that is applied topically to treat genital warts, was approved in 2006. According to FDA, some botanical drugs, including cascara, psyllium, and senna, are undergoing over-the-counter (OTC) drug reviews.

Freddie Ann Hoffman, M.D., founder, HeteroGeneity LCC, explained the two two-step process for getting a drug developed and marketed in the United States involves a Investigational new drug (IND) application, which is obtained prior to conducting trials, and then a New Drug Application (NDA), which shows a drug's safety, efficacy, proper labeling and proper manufacturing methods. The NDA is a much more extensive process than an IND application. "There's not that much confusion getting in an IND, but what my company deals with every day is getting out of IND and into NDA," Hoffman said.

FDA's guidance on botanical drugs removed some hurdles from the IND process because botanicals have history of use in humans, but the guidance did not ease the NDA process.

Hoffman said two NDAs for botanical drugs have been submitted: one is Veregen, and one she can't comment on. "Two submitted and one approved; nota bad batting average," she said.

Blumenthal speculated that the botanical drug regulatory pathway is difficult to understand because it's not easy to get approval. It is, however, easy to start the process, so many ingredients may stay in limbo for years. "It's easier to get into the [botanical] drug approval system, but not easier to get approved," he said. "Many of the same criteria for novel conventional pharmaceutical single-chemical entity drugs apply to the chemically complex botanical drugs." This means it may be difficult to prove safety and efficacy of products that change depending on weather and planting conditions.

Hoffman, who worked at FDA on the botanical drug guidance, said one of the main reasons the low numbers of new botanical drugs is patents. "One of the business reasons is that it's difficult to patent botanical ingredients," she said, giving the example of St. John's wort. "Everyone knows it's good for depression; it's well known and not patentable."

However, Hoffman noted patents are not the whole story, with botanicals.  "There are other equal if not arguably better ways than patents to gain intellectual property and keep a botanical drug proprietary," she said.

On the other hand, McGuffin said companies are investing resources in getting botanical drugs to market. Therefore, those companies with the expertise may not find the regulations difficult to understand.

Drugs vs. Supplements

In September 2012, ABC said sales of herbal dietary supplements in the United States rose by 4.5 percent in 2011. That report estimated 2011's U.S. sales as US$5.3 billion.

Product claims and designated uses are the main distinctions between botanical drugs and botanical supplements. Blumenthal said the formulations of botanical drugs and supplements can be similar.

A botanical drug can claim to treat, prevent, cure, mitigate or diagnose a disease, and a supplement cannot. And, in order to become a botanical drug, the manufacturer/marketer obtain pre-market approval from FDA by submitting an IND application, and then move on to the extensive NDA process to confirm safety and efficacy.