Joanna Cosgrove01.01.07
Ever since the FDA finalized its Investigational New Drug (IND) regulations to help advance ingredients to the human clinical trial stage in 2004, the average number of applications from within the botanical segment have increased steadily each year and now average about between two and three new applications each month.
The IND route has proven tentatively successful for SemBioSys Genetics Inc. of Calgary, AB, Canada. The company's safflower-based insulin product is on track to be approved as a drug. "Insulin is a comparatively simple protein for which an extensive amount of clinical data on safety and efficacy already exists," says the company's Andrew Baum, president and CEO. "Providing that our plant-produced insulin is sufficiently pure and clinically equivalent to commercially available insulin, the meeting confirmed the 505(b)(2) regulatory approach is an appropriate path for approval.
"Demand," he adds, is being "driven by the advent of alternate delivery technologies and the increasing incidence of diabetes," he says, citing that plant-based pharmaceuticals are ultimately less expensive and more scalable.
But applying for IND status doesn't necessarily fast track the relative success of an ingredient, and likewise is the ultimate certainty of ingredients granted New Drug Application (NDA) status after demonstrating that its benefits outweigh its risks. In fact, the entire process is tediously slow and expensive, and few ingredients survive the process, according to Shaw Chen, MD, PhD, associate director for special product review, Botanical Drug Products, for the Office of Drug Evaluation (ODE1) within FDA's Center for Drug Evaluation and Research (CDER), who recently gave a presentation on INDs at a "Developing Botanicals as New Drugs" workshop, which served as a preamble to the 47th Annual Meeting of the American Society of Pharmacognosy in Arlington, VA.
Domestically speaking, Dr. Chen says the IND route is not a viable option for ingredients already on the market. Using ginkgo as an example, he explains that the market is already saturated with ginkgo products, arguing that the public's perception of the ingredient is the same regardless of the brand name or status certification/affiliation listed on the bottle. "We don't see many applications from American dietary supplement companies because there's nothing for them to gain financially," he says. "They are already selling their ingredients. For products already on the market there's not much protection, even if you get NDA approval.
"That's why we see more enthusiasm from the Asians, because they have a different mandate," he continues, noting that the Asian pursuit of IND status is rooted in a proud cultural heritage. "The Asian market wants to legitimately catch up with Westerners on the bio-pharmaceutical front."
Getting through the process can potentially brand an ingredient with bona fide legitimacy, but there are pitfalls that can prevent an ingredient from exiting the process with success. For starters, the process itself is proving to be inexplicably time consuming. "Right now we've only approved one NDA (and) I don't see anything on the horizon. There is no clear reason why and it's very disappointing," says Dr. Chen. "Perhaps people are reluctant to invest more money in the process because it's more of a shotgun approach rather than a guided missile approach.
"Or perhaps they are too carefully plotting their courses of action because chemistry and quality issues are complicated," he says, alluding to the relative irregularity of active ingredients from botanical batch to botanical batch, shipment to shipment.
Dr. Chen says the financial reward is also a gamble. "To illustrate, oatmeal carries a health claim for cardiovascular benefit. A director at General Mills who was responsible for helping push through this claim was asked to give his take on the process. He said he'd never do it again because it didn't benefit General Mills enough; it benefited everyone who had an oatmeal product on the market. General Mills' share didn't increase despite all the work they went through to get that claim approved. The same holds true for botanical ingredients, because the claim benefits everyone who has the same active ingredient. However, if you make it through the IND/NDA process, only you can sell it with that claim."
The IND process is a complicated journey of risk and investment. But the risk hasn't dissuaded those determined to isolate and study ingredients earmarked for cancer and antiviral (AIDS) applications-the number one and number two categories for current IND status. In fact, in the oncology segment alone there are more than 200 applications currently in process.
For more in-depth information on the IND/NDA process, visit http://www.fda.gov/Cder/guidance/4592fnl.pdf to download CDER's Guidance for Industry Botanical Drug products reference pdf.
The IND route has proven tentatively successful for SemBioSys Genetics Inc. of Calgary, AB, Canada. The company's safflower-based insulin product is on track to be approved as a drug. "Insulin is a comparatively simple protein for which an extensive amount of clinical data on safety and efficacy already exists," says the company's Andrew Baum, president and CEO. "Providing that our plant-produced insulin is sufficiently pure and clinically equivalent to commercially available insulin, the meeting confirmed the 505(b)(2) regulatory approach is an appropriate path for approval.
"Demand," he adds, is being "driven by the advent of alternate delivery technologies and the increasing incidence of diabetes," he says, citing that plant-based pharmaceuticals are ultimately less expensive and more scalable.
Common Pitfalls
But applying for IND status doesn't necessarily fast track the relative success of an ingredient, and likewise is the ultimate certainty of ingredients granted New Drug Application (NDA) status after demonstrating that its benefits outweigh its risks. In fact, the entire process is tediously slow and expensive, and few ingredients survive the process, according to Shaw Chen, MD, PhD, associate director for special product review, Botanical Drug Products, for the Office of Drug Evaluation (ODE1) within FDA's Center for Drug Evaluation and Research (CDER), who recently gave a presentation on INDs at a "Developing Botanicals as New Drugs" workshop, which served as a preamble to the 47th Annual Meeting of the American Society of Pharmacognosy in Arlington, VA.
Domestically speaking, Dr. Chen says the IND route is not a viable option for ingredients already on the market. Using ginkgo as an example, he explains that the market is already saturated with ginkgo products, arguing that the public's perception of the ingredient is the same regardless of the brand name or status certification/affiliation listed on the bottle. "We don't see many applications from American dietary supplement companies because there's nothing for them to gain financially," he says. "They are already selling their ingredients. For products already on the market there's not much protection, even if you get NDA approval.
"That's why we see more enthusiasm from the Asians, because they have a different mandate," he continues, noting that the Asian pursuit of IND status is rooted in a proud cultural heritage. "The Asian market wants to legitimately catch up with Westerners on the bio-pharmaceutical front."
Getting through the process can potentially brand an ingredient with bona fide legitimacy, but there are pitfalls that can prevent an ingredient from exiting the process with success. For starters, the process itself is proving to be inexplicably time consuming. "Right now we've only approved one NDA (and) I don't see anything on the horizon. There is no clear reason why and it's very disappointing," says Dr. Chen. "Perhaps people are reluctant to invest more money in the process because it's more of a shotgun approach rather than a guided missile approach.
"Or perhaps they are too carefully plotting their courses of action because chemistry and quality issues are complicated," he says, alluding to the relative irregularity of active ingredients from botanical batch to botanical batch, shipment to shipment.
Dr. Chen says the financial reward is also a gamble. "To illustrate, oatmeal carries a health claim for cardiovascular benefit. A director at General Mills who was responsible for helping push through this claim was asked to give his take on the process. He said he'd never do it again because it didn't benefit General Mills enough; it benefited everyone who had an oatmeal product on the market. General Mills' share didn't increase despite all the work they went through to get that claim approved. The same holds true for botanical ingredients, because the claim benefits everyone who has the same active ingredient. However, if you make it through the IND/NDA process, only you can sell it with that claim."
The IND process is a complicated journey of risk and investment. But the risk hasn't dissuaded those determined to isolate and study ingredients earmarked for cancer and antiviral (AIDS) applications-the number one and number two categories for current IND status. In fact, in the oncology segment alone there are more than 200 applications currently in process.
For more in-depth information on the IND/NDA process, visit http://www.fda.gov/Cder/guidance/4592fnl.pdf to download CDER's Guidance for Industry Botanical Drug products reference pdf.
