Uncertainty over FDA’s NDI guidance has effectively “stalled the innovation” for one botanical supplier, while other firms mull over its implications on solvent extraction techniques.
Just about every segment of the dietary supplements industry has some provision of FDA’s revised new dietary ingredient (NDI) draft guidance to pay special attention to, whether it's probiotic firms considering the need for strain-specific NDI notifications or supplement manufacturers concerned about ingredient combinations in their products. Not to be left out, suppliers of botanical ingredients have their own host of NDI issues to consider in the wake of the revised draft guidance, including FDA’s positions on synthetic botanicals and the use of certain extraction solvents.
At the SupplySide West trade show, Nutritional Outlook caught up with several botanicals firms to get their take on the revised NDI draft guidance. While top concerns varied from firm to firm, there did appear to be some consensus that now is the time to gather together safety and efficacy information, evaluate the best regulatory route forward for each ingredient, and prepare for FDA’s next move.
“Stalled the Innovation”
Take botanicals supplier Cepham (Piscataway, NJ), which is actually holding off on launching several new ingredients until it learns more about the next steps related to FDA’s NDI guidance. Anand Swaroop, PhD, president of Cepham, said the revised NDI draft guidance has actually “stalled the innovation right now.”
“We have three or four products in the pipeline right now,” Swaroop explained. “We won’t launch them until we have the clarity on NDIs and the guidelines are finalized in one way or other.” Cepham will continue its research and product development in the meantime, but all launches are currently on hold, Swaroop said. Before the revised guidance was released, Cepham was actually hoping to pursue Generally Recognized As Safe (GRAS) status for its new ingredients. But because the firm is not looking to sell its ingredients for use in food, the NDI route now seems like the better option, even though it appears to be a “tougher” submission, Swaroop said.
The deadline to submit public comments to FDA regarding the revised NDI guidance falls on December 12, 2016, and industry experts expect it might be at least a few years after that before the agency might release finalized NDI guidance. But Swaroop said Cepham is waiting to see some indication of how the final guidance might develop in the next few months. If timely progress seems unlikely, the company might return to its original plan of pursuing GRAS affirmations.
“If nothing is moving on this by March of next year, we’ll find an alternative solution,” Swaroop said. He added that by that time, “at least we’ll have some clarity on what is happening as far as the lawmaking is concerned. I hope that something happens, or we get some indication that it’s going somewhere. If we have a stalled Congress again, we might just change everything and go with our original plan of filing self-affirmed GRAS.”
Botanical Extraction Techniques
For some botanical ingredient suppliers, one especially concerning provision of the revised NDI draft guidance is its language on the use of certain extraction solvents-namely, supercritical fluid extraction. While the use of solvents such as water or aqueous ethanol for botanical extraction would not require an NDI notification be submitted, extraction solvents such as supercritical CO2-a routine method used to produce many botanical extracts today-would require an NDI notification, according to FDA.
Botanicals firm Euromed (Presto, PA), which supplies saw palmetto extract produced through supercritical extraction, is gathering a body of information on its saw palmetto ingredients so it is prepared if FDA does raise concerns about the ingredients. That includes safety data and analytical information comparing ethanol-extracted saw palmetto with supercritical CO2–extracted saw palmetto, explained Guy Woodman, director of sales for Euromed.
“We have a dossier of information available in the event that there is a question from FDA regarding the products,” said Woodman. “That would be the first avenue that we would want to take-try to satisfy FDA’s concerns about the product in terms of the safety and the different characteristics of the product versus a material that has a long history of use,” such as ethanol-extracted saw palmetto.
The first goal is to demonstrate to FDA that ingredients produced through supercritical extraction are safe, Woodman said. Then, if necessary, that information could be put toward preparing a GRAS affirmation or NDI notification. At the moment, Euromed favors the GRAS approach because it allows for use in both food items and dietary supplements, according to Woodman.
An unfortunate consequence of FDA’s stance on extraction solvents is that it could make supercritical CO2 a less attractive option than botanical extraction with water, hexane, or ethanol, since the latter methods would not require an NDI submission, noted Benjamin Lightburn, president of Mazza Innovation (Delta, British Columbia, Canada).
“The question of supercritical CO2 is an interesting one,” Lightburn told Nutritional Outlook. “On the one hand, nobody would argue that it is worse for human health than extraction with hexane. On the other hand, the draft guidance specifically mentions it as a process that would require NDI notification. I hope that in future guidance FDA will provide more of their thinking in that respect.”
Lightburn said he believes Mazza’s proprietary extraction process PhytoClean will not be subject to NDI notification as it is a water-based method. Lightburn added that PhytoClean does not concentrate extracted herbs to such a degree that it significantly alters the chemical composition of the herbs, although Mazza would like FDA to provide further guidance on exactly how much concentration is permitted before FDA considers it a chemical alteration.
On a separate but related note, Mazza’s facility in British Columbia where the PhytoClean method is employed was recently registered as a Good Manufacturing Practices (GMP) facility by NSF International (Ann Arbor, MI), a development Lightburn hailed as a “significant company milestone.”
Meanwhile, to the question of whether the revised NDI draft guidance is turning people away from supercritical CO2 extraction, Euromed’s Woodman says he has not found it to be an enormous area of concern among customers.
“At this moment in time I have had people ask about it, but it’s not something where I’ve had anybody in the course of the last couple years say they wouldn’t use the product because of that concern,” Woodman said. However, he noted that as the NDI guidance becomes finalized and an actual implementation date approaches, more companies may start raising concerns about certain extraction solvents.
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