I hate waitingfor a subway train; for my wife to get ready; for FDA to re-release its revised guidance on new dietary ingredients (NDIs). But my question is, will we make productive use of that time?
Take the NDI issue. FDA has promised a revised guidance that takes into account the voluminous concerns expressed by the industry in our written comments and four separate face-to-face meetings with the agency over a year. What are you doing while you wait?
I fear that many firms have decided that until a new guidance is issued, they can basically ignore the NDI requirements of DSHEA. They do that at their own peril. Companies should appreciate that the requirement to file a notification when they bring a new ingredient to market is enshrined in DSHEA itself-regardless of the status of a guidance, the law is still the law.
One company recently discovered that the hard way. In a warning letter to Star Scientific, released by the agency last month, FDA announced that the ingredient anatabine is no longer a viable dietary ingredient because the company failed to file its NDI notification in a timely manner. Heres how the events played out: FDA acknowledges that the company began selling products containing anatabine in 2010, but Star Scientific did not file an NDI notice for the ingredient. It is also undisputed that another firm filed an Investigational New Drug (IND) application for anatabine in 2012.
[Not to be confused, an IND application is required to study the drug properties of a substance in most human clinical trials; an NDI notification is a notice to FDA at least 75 days in advance of marketing that a firm is bringing a new dietary ingredient to market and that it has data establishing a reasonable expectation of safety in the ingredient and the products in which it will be used.]
Heres the rub: A separate provision of DSHEA states that an ingredient may not be marketed as a dietary supplement if the article has been authorized for investigation as a new drug for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public. 21 USC §321(ff)(3)(B)(ii). In other words, once the ingredient is seriously investigated as a drug, it cant be used in a dietary supplement unless it was marketed in the supplement first. Even though Star was first to market, FDA contends that the failure to file an NDI notification means that it was not legally marketed, and thus, the IND application trumps Star Scientific.
And the ingredient is removed from the dietary supplement marketfor all manufacturers and marketers, end of story. All of which illustrates why its so important for firms to file their NDI notices even as we wait for the next draft of the guidance.
In fairness to Star, another issue is involved here too; namely whether a constituent of a food that is subsequently extracted and concentrated can be considered as marketed as food prior to 1994, and thus be considered a grandfathered ingredient that doesnt require an NDI notice. FDA concedes that anatabine occurs naturally in foods such as cauliflower, eggplant, potatoes and tomatoes, but it maintains that anatabine itself was not used as an article for food prior to 1994. According to the agency, its mere presence in small quantities in the plant doesnt assure that it is a grandfathered ingredient. This same argument arose in the contexts of dimethylamylamine (DMAA), dendrobium, and agelineback when we were still asking whether those substances actually were constituents of various botanicals. It was easy to allow FDA to take this position if it helped get potentially dangerous amphetamine-like stimulants off the market. Now that it has implications for other ingredients, this issue takes new concern.
So heres my point: regardless of what FDA provides in the new and improved draft NDI Guidance, there will still be substantive issues to be resolved, and in the meantime, the actual requirement to file a notification for all new ingredients comes from the text of DSHEA itself, not a guidance. Ignoring the law can have some costly and irreversible implications for all of us. How are you spending your time waiting for FDA?
CRN and Virgo will co-host a webinar on Wednesday, January 29th, NDIs Now: What You Need to Ensure Compliance to explore how firms should be implementing the NDI requirements of DSHEAwith or without the anticipated FDA guidance.